WO2022159650A1

WO2022159650A1 - HETEROBIFUNCTIONAL COMPOUNDS AS DEGRADERS OF eEF1A2

Info

Publication number: WO2022159650A1
Application number: PCT/US2022/013225
Authority: WO
Inventors: Jian Jin; Kabir, Md; Ning Sun; H. Umit KANISKAN
Original assignee: Icahn School Of Medicine At Mount Sinai
Priority date: 2021-01-22
Filing date: 2022-01-21
Publication date: 2022-07-28

Abstract

Disclosed are eukaryotic translation elongation factors 1 alpha 2 (eEF1A2) or perinucleolar compartment (PNC)-related metastatic protein degradation / disruption compounds including an eEF1A2 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of eEF1A2-mediated diseases as well as PNC-related diseases.

Description

HETEROBIFUNCTIONAL COMPOUNDS AS DEGRADERS OF eEF1A2 FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under T32 CA078207 awarded by the National Institutes of Health, NIH T32 Training Grant, (NIH).5 The government has certain rights in the invention. TECHNICAL FIELD This disclosure relates to bivalent compounds (e.g., heterobifunctional compounds) which degrade and/or disrupt eukaryotic translation elongation factors 1 alpha 2 (eEF1A2) or perinucleolar compartment (PNC)-related metastatic protein, compositions comprising one or more of the bivalent compounds, and methods of use thereof for the treatment of eEF1A2 or PNC- mediated diseases in a subject in need thereof. The disclosure also relates to methods for designing such bivalent compounds. BACKGROUND OF THE INVENTION Protein translation factors are essential players involved in the complex regulation of protein synthesis. The eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are important component of the translation machinery and deliver the aminoacyl-tRNA to the amino (A) site of the ribosome during elongation ^[1]. Albeit eEF1A1 shares 98% amino acid identity with eEF1A2, they have different chromosomal location and the latter has a weaker affinity towards GDP ^[2]. Furthermore, eEF1A1 is expressed in majority of the cell types while eEF1A2 is primarily expressed in non-dividing terminally differentiated cells such as neurons and cardiomyocytes^[2]. Dysregulation of eEF1A2 has been linked to increased proliferation and tumorigenicity of several types of cancer and identified as a oncoprotein. High expression of eEF1A2 has been reported in breast, ovarian, lung, and liver cancer, and often leads to poor prognosis. Particularly, more than 80% of pancreatic cancer cells have an overexpression of eEF1A2 while normal pancreas has very low expression level^[3]. It was shown that the invasion and migration properties for different pancreatic cancer cell lines is directly proportional to the expression levels of eEF1A2^[4]. Furthermore, overexpression of eEF1A2 can lead to increased metastatic tumors in- vivo and silencing eEF1A2 can significantly reduce metastasis^[5]. Experimental studies have shown that eEF1A2 can form a complex with RNA-activated protein kinase (PKR) and inhibit pro-apoptotic activity^[6]. Additionally, eEF1A2 can also activate the PI3K- AKT-mTOR pathway to stabilize MDM4 and inhibit p53 functionality^[7]. Finally, RAS- driven cancer such as pancreatic cancer can activate methyltransferase-like 13 (METTL13) to enhance the activity of eEF1A2 to increase protein translational output^[8] ^[9]. Therefore, eEF1A2 can be targeted to impede cancer survival, proliferation and metastasis. It was shown that ML246 (Metarrestin) can disassemble perinuclear compartment (PNC) and block metastatic development in mouse models of human cancers partly by binding strongly to eEF1A2^{[10] [11] [12]}. Currently, Metarrestin is entering clinical trials for treatment against metastatic solid tumors such as pancreatic cancer^[13]. However, Metarrestin induced hypoactivity, seizure-like events and ataxia in preclinical beagle dog models when orally administered possibly due to inhibition of eEF1A2 normal function in the brain. Metarrestin show good penetration ability could across the blood brain barrier which may cause a certain degree of side effects and disadvantages^[14]. Therefore, new and better therapeutics are necessary to inhibit tumor growth and block the rise of metastasis without any central nervous system (CNS) toxicity. PROTACs are heterobifunctional molecules which offer a new platform for chemical degradation of intended protein ^{[15] [16]}. With one ligand for the protein of interest and another ligand to recruit E3 ubiquitin ligase joined together by a linker, PROTACs can effectively polyubiquitinate at specific lysine residues and degrade protein of interest (POI) despite low binding affinity^[16]. Several structural studies on POI-PROTAC revealed that there is a ternary complex formation with the Cullin–RING E3 ligases to form a linked U-shaped complexes in which the substrate-binding element such as von Hippel-Lindau (VHL) or cereblon (CRBN) directly interacting with the RING-domain protein RBX1^[15]. This U shape ternary complex allows for targeted ubiquitin transfer by the proximal positioning of the ubiquitin conjugated-E2 and POI. One of the main advantages of PROTACs over traditional small-molecule inhibitors are that PROTACs can completely degrade the target protein and can be effectively recycled back which removes the need for continuous drug treatment. Another advantage of PROTAC is the enhanced degradation selectivity towards target protein compared to parent inhibitor shown by kinase degraders^{[17] [18]}. Unlike traditional small molecule which binds to active site of a protein, PROTAC operates by event-driven mechanism of action and can effectively degrade proteins lacking a catalytic activity or scaffold proteins. Thus, PROTACs could potentially overcome some point-mutation based drug resistance^[19]. Furthermore, PROTAC showed promising in-vivo pharmacokinetics (PK) properties and due to their large molecular weight (MW), they are unlikely to penetrate the blood brain barrier (BBB) and cause any CNS toxicity^{[20] [21] [22]}. Therefore, PROTACs have garnered significant interest from the biomedical and drug discovery community as an emerging class of novel therapeutic approaches. We have developed first-in-class eEF1A2 PROTAC degraders based on Metarrestin and determined that they effectively degrade eEF1A2 in cancer cells despite PNC variability and reduce the proliferation and growth of pancreatic, prostate and breast cancer cells in vitro. SUMMARY OF THE INVENTION The present disclosure relates generally to bivalent compounds (e.g., bi-functional compounds) which degrade and/or disrupt eEF1A2 and to methods for the treatment of eEF1A2-mediated diseases (i.e., a disease which depends on eEF1A2; overexpresses eEF1A2; depends on eEF1A2 activity; or includes elevated levels of eEF1A2 activity relative to a wild-type tissue of the same species and tissue type). It is important to note, because the eEF1A2 degraders/disruptors have dual functions (enzyme inhibition plus protein degradation/disruption), the bivalent compounds of the present disclosure can be significantly more effective therapeutic agents than currently available eEF1A2 inhibitors, which inhibit the enzymatic activity of eEF1A2, but do not affect eEF1A2 protein levels. The present disclosure further provides methods for identifying eEF1A2 degraders/disruptors as described herein. More specifically, the present disclosure provides a bivalent compound including an eEF1A2 ligand conjugated to a degradation/disruption tag. In some aspects, the eEF1A2 degraders/disruptors have the form “PI-linker- EL”, as shown below: PI Linker EL

comprises an eEF1A2 ligand (e.g., an eEF1A2 inhibitor) and EL (E3 ligase) comprises a degradation/disruption tag (e.g., E3 ligase ligand). Exemplary eEF1A2 ligands (PI), exemplary degradation/disruption tags (EL), and exemplary linkers (Linker) are illustrated below: eEF1A2 Ligands In one refinement, eEF1A2 ligands (PI) comprise a moiety of FORMULA 1:

wherein, the “Linker” moiety of the bivalent compound is attached to Z; as indicated by the dotted line; X is selected from NH or O or S In an embodiment, R¹ is selected from the following:

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰ at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)₂R¹¹, S(O)₂NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1- C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Wherein; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1- C8 alkylaminoC1- C8 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C₈ cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH- CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl optionally substituted C₁-C₈ haloalkyl optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 2:

FORMULA 2 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH- CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl optionally substituted aryl optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 3:

FORMULA 3 wherein, the “Linker” moiety of the bivalent compound is attached to N as indicated by the dotted line; X is selected from NH or O or S; Z is selected from N or CH The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 4:

_{FORMULA 4} _wherein, _{the “Linker” moiety of the bivalent compound is attached to N as indicated by the dotted} _line; _{X is selected from NH or O or S;} _{Z is selected from N or CH} _{The definitions of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R17, R18, R19, R20 are the same} _{as for FORMULA 1} _{m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and} _{W and Q, at each occurrence, are independently selected from null, CO, CO2, CH2, NH,} _{NH-CO, CO-NH, CH2-NH-CO, CH2-CO-NH, NH-CO-CH2, CO-NH-CH2, CH2-NH-} _{CH2-CO-NH, CH2-NH-CH2-NH-CO, -CO-NH, CO-NH- CH2-NH-CH2, CH2-NH-CH2,} _{CR21R22, C(O)NR21 , C(S)NR21, O, S, SO, SO2, SO2NR21, NR21, NR21CO,} _{NR21CONR22, NR21C(S), optionally substituted C1-C8 alkyl, optionally substituted} _{C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted} _{C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted} _{C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8} _{membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted} _{3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted} _{heteroaryl, optionally substituted C3-C13 fused cycloalkyl, optionally substituted C3-} _{C13 fused heterocyclyl, optionally substituted C3-C13 bridged cycloalkyl, optionally} _{substituted C3-C13 bridged heterocyclyl, optionally substituted C3-C13 spiro cycloalkyl,} _{and optionally substituted C3-C13 spiro heterocyclyl; wherein R21 and R22 are} _{independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally} _{substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy,} _{optionally substituted 3-8 membered heterocyclyl, optionally substituted C1-C8 alkoxy,} _{optionally substituted C1-C8 alkoxyalkyl, optionally substituted C1-C8 haloalkyl,} _{optionally substituted C1-C8 hydroxyalkyl, optionally substituted C1-C8 alkylamino,} _{and optionally substituted C1-C8 alkylamino C1-C8 alkyl;} and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 5:

FORMULA 5 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO₂, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 6: Ph Ph HN

FORMULA 6 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH-CH₂-CO- NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl optionally substituted C₃-C₁₃ spiro cycloalkyl and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C1- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 6A and FORMULA 6B: Ph Ph

FORMULA 6A Ph Ph HN 0

FORMULA 6B wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line ; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH-CH₂-CO- NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ C(S)NR²¹ O S SO SO₂ SO₂NR²¹ NR²¹ NR²¹CO NR²¹CONR²² NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-C13 fused cycloalkyl, optionally substituted C3-C13 fused heterocyclyl, optionally substituted C3-C13 bridged cycloalkyl, optionally substituted C3-C13 bridged heterocyclyl, optionally substituted C3-C13 spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁- C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. Degradation/Disruption Tags Degradation/Disruption tags (EL) include, but are not limited to: In an embodiment, degradation/disruption tags include a moiety according to FORMULAE 12A, 12B, 12C and 12D:

FORMULA 12A FORMULA 12B FORMULA 12C FORMULA 12D, wherein V, W, and X are independently selected from CR² and N; Y is selected from CO, CR³R⁴, and N=N; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C₁-C₁₀ alkylene, optionally substituted C₁-C₁₀ alkenylene, optionally substituted C₁-C₁₀ alkynylene, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferly, Z is selected from null, CH₂, CH=CH, C C, NH and O; R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl. In an embodiment, degradation/disruption tags include a moiety according to one of FORMULAE 12E, 12F, 12G, 12H, and 12I:

FORMULA 12E FORMULA 12F FORMULA 12G

FORMULA 12H FORMULA 12I wherein U, V, W, and X are independently selected from CR² and N; Y is selected from CR³R⁴, NR³ and O; preferably, Y is selected from CH2, NH, NCH3 and O; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C1-C10 alkylene, optionally substituted C1-C10 alkenylene, optionally substituted C1-C10 alkynylene, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C3-C13 bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferably, Z is selected from null, CH₂, CH=CH, c≡ c, NH and O; R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C1-C6 alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and pharmaceutically acceptable salts thereof. In an embodiment, degradation/disruption tags include a moiety according to FORMULA 13A:

FORMULA 13A, wherein R¹ and R² are independently selected from hydrogen, optionally substituted C₁- C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; and R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)C₃- C₇ cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl, optionally substituted C(O)OC₁-C₈ hydroxyalkyl, optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C₇ cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC1- C8alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC1- C8 hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)NC₃-C₇ cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)2, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)2. In an embodiment, degradation/disruption tags include a moiety according to FORMULAE 13B, 13C, 13D, 13E and 13F: 15

FORMULA 13D FORMULA 13E FORMULA 13F wherein R¹ and R² are independently selected from hydrogen, halogen, OH, NH₂, CN, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC1- C8alkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; (preferably, R¹ is selected from iso-propyl or tert-butyl; and R² is selected from hydrogen or methyl); R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)C₃- C7 cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl, optionally substituted C(O)OC₁-C₈ hydroxyalkyl, optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C₇ cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC1- C8alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC1- C8 hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)NC₃-C7 cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)2, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)2; and R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO2R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC1- C8alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl and optionally substituted heteroaryl; or R⁴ and R⁵; R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; Ar is selected from aryl and heteroaryl, each of which is optionally substituted with one or more substituents independently selected from F, Cl, CN, NO₂, OR⁸, NR⁸R⁹, COR⁸, CO2R⁸, CONR⁸R⁹, SOR⁸, SO₂R⁸, SO₂NR⁹R¹⁰, NR⁹COR¹⁰, NR⁸C(O)NR⁹R¹⁰, NR⁹SOR¹⁰, NR⁹SO₂R¹⁰, optionally substituted C₁-C₆ alkyl, optionally substituted C₁-C₆ alkoxyalkyl, optionally substituted C₁-C₆ haloalkyl, optionally substituted C₁-C₆ hydroxyalkyl, optionally substituted C₁-C₆alkylaminoC1- C6alkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₆ alkenyl, optionally substituted C₂-C₆ alkynyl, optionally substituted aryl, and optionally substituted C4-C5 heteroaryl; wherein R⁸, R⁹, and R¹⁰ are independently selected from null, hydrogen, optionally substituted C₁-C₆ alkyl, optionally substituted C₂-C₆ alkenyl, optionally substituted C2- C6 alkynyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁸ and R⁹; R⁹ and R¹⁰ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; and pharmaceutically acceptable salts thereof. In an embodiment, degradation/disruption tags include a moiety according to FORMULA 14A:

, wherein V, W, X, and Z are independently selected from CR⁴ and N; R¹, R², R³, and R⁴ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl. In an embodiment, degradation/disruption tags include a moiety according to FORMULA 14B:

FORMULA 14B, wherein R¹, R², and R³ are independently selected from hydrogen, halogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO2R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted aryl-C₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁- C₈alkylaminoC₁-C₈alkyl optionally substituted 3-8 membered cycloalkyl optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; and pharmaceutically acceptable salts thereof. In an embodiment, degradation/disruption tags are selected from the group consisting of:

;

and pharmaceutically acceptable salts thereof. LINKERS In any of the above-described compounds, the EEF1A2 ligand can be conjugated to the degradation/disruption tag through a linker The linker can include e.g., acyclic or cyclic saturated or unsaturated carbon, ethylene glycol, amide, amino, ether, urea, carbamate, aromatic, heteroaromatic, heterocyclic, and/or carbonyl containing groups with different lengths. In an embodiment, the linker is a moiety according to FORMULA 16:

FORMULA 16, 10 wherein A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR¹, C(S)NR¹, O, S, SO, SO₂, SO₂NR¹, NR¹, NR¹CO, NR¹CONR², NR¹C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy,optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R¹ and R² are independently selected from hydrogen, optionally substituted C₁- C8 alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted 3-8 membered cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; and m is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16A:

FORMULA 16A, wherein R¹, R², R³, and R⁴, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR⁵, C(S)NR⁵, O, S, SO, SO₂, SO₂NR⁵, NR⁵, NR⁵CO, NR⁵CONR⁶, NR⁵C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R⁵ and R⁶ are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; m is 0 to 15; n, at each occurrence, is 0 to 15; o is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16B:

FORMULA 16B, wherein R¹ and R², at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C1- C8alkylaminoC₁-C₈alkyl; A and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR³, C(S)NR³, O, S, SO, SO₂, SO₂NR³, NR³, NR³CO, NR³CONR⁴, NR³C(S), and optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃- C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, or C₃-C₁₃ spiro heterocyclyl; wherein R³ and R⁴ are independently selected from hydrogen, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃- C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C₁-C₈alkylaminoC₁-C₈alkyl; each m is 0 to 15; and n is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16C:

FORMULA 16C, wherein X is selected from O, NH, and NR⁷; R¹, R², R³, R⁴, R⁵, and R⁶, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl optionally substituted C₃-C₈ cycloalkoxy optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A and B, at each occurrence, are independently selected from null, CO, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CO2, C(O)NR⁷, C(S)NR⁷, O, S, SO, SO₂, SO₂NR⁷, NR⁷, NR⁷CO, NR⁷CONR⁸, NR⁷C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R⁷ and R⁸ are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; m, at each occurrence, is 0 to 15; n, at each occurrence, is 0 to 15; o is 0 to 15; and p is 0 to 15; and pharmaceutically acceptable salts thereof In an embodiment, the linker is selected from the group consisting of a ring selected from the group consisting of a 3 to 13 membered ring; a 3 to 13 membered fused ring; a 3 to 13 membered bridged ring; and a 3 to 13 membered spiro ring; and pharmaceutically acceptable salts thereof. In an embodiment, the linker is a moiety according to one of FORMULAE C1, C2, C3, C4 and C5: FORMULA C1,

10 FORMULA C2,

FORMULA C₃,

FORMULA C4, and

FORMULA C5; and p

a aceu ca y accep a e sa s e eo . In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS106-033, NS106-034, NS106-035, NS106-036, NS106-037, NS106-038, NS106-039, NS106-084, NS106-085, NS106-086, NS106- 087, NS106-088, NS113-167, NS106-094, NS106-040, NS106-041, NS106-042, NS106-043, NS106-044, NS106-045, NS106-046, NS106-047, NS106-048, NS106- 049, NS113-044, NS113-045, NS113-046, NS113-047, NS113-048, NS113-049, NS113-050, NS113-051, NS113-052, NS113-053, NS113-054, NS113-055, NS113- 056, NS113-057, NS113-058, NS113-059, NS113-060 and NS113-061; and pharmaceutically acceptable salts thereof. In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS106-051, NS106-052, NS106-053, NS106-054, NS106-055, NS106-056, NS106-057, NS106-058, NS106-059, NS106-060, NS106- 061, NS106-078, NS106-079, NS106-096, NS106-080, NS106-081, NS106-082, NS106-083, NS106-111, NS113-168, NS106-065, NS106-066, NS106-067, NS106- 068, NS106-069, NS106-070, NS106-071, NS106-072, NS106-073, NS106-074, NS113-093, NS106-075, NS113-094, NS106-076, NS113-095, NS113-096, NS106- 077, NS113-028, NS113-029, NS113-030, NS113-031, NS113-032, NS113-033, NS113-034, NS113-083, NS113-084, NS113-085, NS113-086, NS113-087, NS113- 039, NS113-040, NS113-041, NS113-042, NS113-043, NS113-088, NS113-089, NS113-090, NS113-091 and NS113-092; and pharmaceutically acceptable salts thereof. In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS113-075, NS113-076, NS113-077, NS113-078, NS113-079, NS113-080, NS113-081 and NS113-082; and pharmaceutically acceptable salts thereof. In one embodiment, preferred compounds according to the present invention include: a. N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N9-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)nonanediamide (NS106-070). b. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((6-((6-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)amino)-6-oxohexyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-043). c. (2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-((S)-3-((12-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamido)dodecyl)amino)-1-(4-(4-methylthiazol-5- yl)phenyl)-3-oxopropyl)pyrrolidine-2-carboxamide (NS113-054). d. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((2-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)ethyl)amino)-2-oxoethoxy)- 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-055). e. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((3-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)propyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-056) f. (2S,4R)-1-((S)-2-(tert-butyl)-21-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)-4,14-dioxo-6,9,12-trioxa-3,15-diazahenicos-20-ynoyl)-4- hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-094). g. N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N17-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12,15- pentaoxaheptadecanediamide (NS113-096). In one embodiment, preferred compounds according to the present invention include: a. 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS106-078). b. 3-(4-(5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)amino)pent-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (NS113- 168). In one embodiment, preferred compounds according to the present invention include: a. (3r,5r,7r)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)adamantane-1-carboxamide (NS121-135). b. 2-((3r,5r,7r)-adamantan-1-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS121-136). In some aspects, this disclosure provides a method of treating the eEF1A2- mediated diseases, the method including administering to a subject in need thereof with an eEF1A2-mediated disease one or more bivalent compounds including an eEF1A2 ligand conjugated to a degradation/disruption tag. The eEF1A2-mediated diseases may be a disease resulting from eEF1A2 amplification. The eEF1A2- mediated diseases can have elevated eEF1A2 activity relative to a wild-type tissue of the same species and tissue type. Non-limiting examples of eEF1A2-mediated diseases or diseases whose clinical symptoms could be treated by eEF1A2 degraders/disruptors-mediated therapy include: all solid and liquid cancer, chronic infections that produce exhausted immune response, infection-mediated immune suppression, age-related decline in immune response, age-related decline in cognitive function and infertility. Exemplary types of cancer that could prevented, or therapeutically treated by manipulation of eEF1A2 level by degraders/disruptors should include all solid and liquid cancers, including, but not limited to, cancers of the breast, respiratory tract, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Examples of liquid cancers include lymphomas, sarcomas, and leukemias. Listed below are the type of cancers that immunotherapy using eEF1A2 degraders/disruptors should be able to prevent or treat. Examples of breast cancers include, but are not limited to, triple negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ. Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non- small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma. Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer. Tumors of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus. Examples of ovarian cancer include, but are not limited to, serous tumor, endometrioid tumor, mucinous cystadenocarcinoma, granulosa cell tumor, Sertoli- Leydig cell tumor and arrhenoblastoma. Examples of cervical cancer include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumor, glassy cell carcinoma and villoglandular adenocarcinoma. Tumors of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancers. Examples of esophageal cancer include, but are not limited to, esophageal cell carcinomas and adenocarcinomas, as well as squamous cell carcinomas, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma and lymphoma. Examples of gastric cancer include, but are not limited to, intestinal type and diffuse type gastric adenocarcinoma. Examples of pancreatic cancer include, but are not limited to, ductal adenocarcinoma, adenosquamous carcinomas and pancreatic endocrine tumors. Example of tumors of the urinary tract include, but are not limited to, bladder, penile kidney renal pelvis ureter urethral and human papillary renal cancers Examples of kidney cancer include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (reninoma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear-cell sarcoma of the kidney, mesoblastic nephroma and Wilms' tumor. Examples of bladder cancer include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma and small cell carcinoma. Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma. Examples of liver cancers include, but are not limited to, hepatocellular carcinoma (liver cell carcinomas with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma. Example of skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non- melanoma skin cancer. Example of head-and-neck cancers include, but are not limited to, squamous cell cancer of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer and squamous cell. Example of lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system. Example of sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma. Example of leukemias include, but are not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. The eEF1A2 degraders/disruptors should be able to treat the above cancer types as stand alone agents or used as an agent in combination with existing standards of treatment therapy and other FDA-approved cancer therapy. Therapeutic use of eEF1A2 extends to include diseases and therapies that are amenable to treatment by stimulation/augmentation of immune response, including the prolongation of immune responses during vaccination for immunizable diseases such as influenza and coronaviruses, including Covid 19. Also, because eEF1A2 is expressed at high level in other anatomical locations – such as testes – the eEF1A2 degraders/disruptors should be able to treat or prevent diseases related to testes that were caused by eEF1A2 or could be treated by eEF1A2 degraders/disruptors. Therapeutic use of eEF1A2 degraders further extends to include therapies involving ex vivo treatment of immune cells, including, but not limited to, all T cell subsets, genetically engineered T cells, Chimeric Antigen Receptor (CAR) T cells, tumor infiltrating lymphocytes, dendritic cells, macrophage, mast cells, granulocytes (include basophils, eosinophils, and neutrophils), natural killer cells, NK T cells and B cells. Such cells would be therapeutically treated by eEF1A2 degraders and then re- introduced back to the patient being treated for conditions that would benefit from reduction in eEF1A2 expression. The sources of cells for such ex vivo treatment include, but are not limited to, the autologous bone marrow cells from the patient him/herself, or from the patient’s frozen banked cord blood stem cells, peripheral blood or bone marrow stem cells from MHC-matched or MHC-mismatched donors. Treating patients by administering specific immune cells that had been treated with eEF1A2 degraders offers many added advantages over in vivo use. By treating specific immune cells type with eEF1A2 degraders ex vivo, it is possible to specifically target the immune cell type that would receive the benefit of having the endogenous eEF1A2 level reduced by eEF1A2 degraders while sparing the eEF1A2 expression level in other immune cell types that are not involved in the disease condition. This therapeutic approach would provide cell type-specific targeting of immune cells in a way that is not possible with the use of eEF1A2 degrader in the in vivo setting Thus, the ex vivo approach would likely limit potential toxicity that may result from reduction of HPK1 level in immune cell types that do not benefit from a reduction in eEF1A2 levels. Furthermore, by administering eEF1A2 degraders in the ex vivo cell setting, the risk of patients experiencing the toxicity or undesirable outcome that might occur should the eEF1A2 degraders were to be administered systemically would be eliminated. It is known that eEF1A2 is also expressed in non-hematopoietically-derived tissues such as the brain and testes. Because of this tissue-specific expression pattern of eEF1A2, eEF1A2 degraders might be able to treat or prevent diseases related to the testes that were caused by eEF1A2. The use of eEF1A2 expression status of the tumor as the biomarker would enable stratification of patients into appropriate therapeutic groups that would receive eEF1A2 degraders in vivo or ex vivo, based on eEF1A2 expression in the tumors. Furthermore, using eEF1A2 degraders in an ex vivo setting offers additional advantages over gene-editing approaches such as CRISPR in that it allows therapeutic use of eEF1A2 degraders as a non-permanent treatment that allows a therapeutic regimen to be adjusted temporally through dosing levels and through alteration of the administration schedule. In addition, eEF1A2 degraders could be used in settings whereby stimulation/augmentation of the immune response is required, or when the prolongation of immune responses is needed. Improving immune response to vaccination is one of the settings in which eEF1A2 degraders could be used therapeutically. eEF1A2 degraders could also be used to enhance the antigen presentation capability of dendritic cell-based cancer vaccines. Other utilities of eEF1A2 degraders include treatment of dendritic cells with eEF1A2 degraders to increase resistance to maturation-induced apoptosis, thus increasing the yield of dendritic cell production. In any of the above-described methods, the bivalent compounds can be NS106-033, NS106-034, NS106-035, NS106-036, NS106-037, NS106-038, NS106-039, NS106- 084, NS106-085, NS106-086, NS106-087, NS106-088, NS113-167, NS106-094, NS106-040, NS106-041, NS106-042, NS106-043, NS106-044, NS106-045, NS106- 046, NS106-047, NS106-048, NS106-049, NS113-044, NS113-045, NS113-046, NS113-047, NS113-048, NS113-049, NS113-050, NS113-051, NS113-052, NS113- 053, NS113-054, NS113-055, NS113-056, NS113-057, NS113-058, NS113-059, NS113-060, NS113-061, NS106-051, NS106-052, NS106-053, NS106-054, NS106- 055, NS106-056, NS106-057, NS106-058, NS106-059, NS106-060, NS106-061, NS106-078, NS106-079, NS106-096, NS106-080, NS106-081, NS106-082, NS106- 083, NS106-111, NS113-168, NS106-065, NS106-066, NS106-067, NS106-068, NS106-069, NS106-070, NS106-071, NS106-072, NS106-073, NS106-074, NS113- 093, NS106-075, NS113-094, NS106-076, NS113-095, NS113-096, NS106-077, NS113-028, NS113-029, NS113-030, NS113-031, NS113-032, NS113-033, NS113- 034, NS113-083, NS113-084, NS113-085, NS113-086, NS113-087, NS113-039, NS113-040, NS113-041, NS113-042, NS113-043, NS113-088, NS113-089, NS113- 090, NS113-091, NS113-092, NS113-075, NS113-076, NS113-077, NS113-078, NS113-079, NS113-080, NS113-081, NS113-082, NS121-135, NS121-136, NS121- 137, NS121-138, NS121-139, NS121-140, NS121-141, NS121-142 or analogs thereof. In some aspects of the disclosed methods, the bivalent compounds can be administered by any of several routes of administration including, e.g., orally, parenterally, intradermally, subcutaneously, topically, and/or rectally. Any of the above-described methods can further include treating the subject with one or more additional therapeutic regimens for treating cancer. The one or more additional therapeutic regimens for treating cancer can be, e.g., one or more of surgery, chemotherapy, radiation therapy, hormone therapy, or immunotherapy. This disclosure additionally provides a method for identifying a bivalent compound which mediates degradation/disruption of eEF1A2, the method including providing a heterobifunctional test compound including an eEF1A2 ligand conjugated to a degradation/disruption tag, contacting the heterobifunctional test compound with a cell (e.g., a cancer cell such as an eEF1A2-mediated cancer cell) including a ubiquitin ligase and eEF1A2. [RCSJ1]Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows cell viability screening of top metarrestin based eEF1A2 degraders in cell lines of variable PNC levels such as MDA-MB-231 (low PNC), and PC-3M (high PNC). Figure 2 shows a Western blot analysis showing that metarrestin based eEF1A2 degraders could reduce the endogenous level of eEF1A2 in MDA-MB-231, PANC1 and PC-3M cell lines. Figure 3 shows a Western blot analysis showing the time-dependent degradation of eEF1A2 using metarrestin based degraders in PANC-1 cell lines, while the negative analogue of VHL-based degrader could not degrader eEF1A2 in either MDA-MB-231 or PANC1 cell lines. Figure 4 shows dose-dependent degradation was observed by Metarrestin-based degraders in PANC-1 cell line after 24h treatment. DETAILED DESCRIPTION The present disclosure is based, in part, on the discovery that novel heterobifunctional molecules which degrade eEF1A2, eEF1A2 fusion proteins, and/or eEF1A2 mutant proteins are useful in the treatment of eEF1A2-mediated diseases. Non-limiting examples of eEF1A2-mediated diseases or diseases whose clinical symptoms could be treated by eEF1A2 degraders/disruptors-mediated therapy include: all solid and liquid cancer, chronic infections that produce exhausted immune response, infection-mediated immune suppression, age-related decline in immune response, age- related decline in cognitive function and infertility Exemplary type of cancers that could be prevented, or therapeutically treated by manipulation of eEF1A2 level by degraders/disruptors should include all solid and liquid cancers, including, but not limited to, cancers of the breast, respiratory tract, , reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Examples of liquid cancers include lymphomas, sarcomas, and leukemias. Listed below are the type of cancers that immunotherapy using eEF1A2 degraders/disruptors should be able to prevent or treat. Examples of breast cancers include, but are not limited to, triple negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ. Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non- small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma. Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer. Tumors of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus. Examples of ovarian cancer include, but are not limited to, serous tumor, endometrioid tumor, mucinous cystadenocarcinoma, granulosa cell tumor, Sertoli- Leydig cell tumor and arrhenoblastoma. Examples of cervical cancer include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumor, glassy cell carcinoma and villoglandular adenocarcinoma. Tumors of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancers. Examples of esophageal cancer include, but are not limited to, esophageal cell carcinomas and adenocarcinomas, as well as squamous cell carcinomas, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma and lymphoma. Examples of gastric cancer include, but are not limited to, intestinal type and diffuse type gastric adenocarcinoma. Examples of pancreatic cancer include, but are not limited to, ductal adenocarcinoma, adenosquamous carcinomas and pancreatic endocrine tumors. Example of tumors of the urinary tract include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral and human papillary renal cancers. Examples of kidney cancer include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (reninoma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear-cell sarcoma of the kidney, mesoblastic nephroma and Wilms' tumor. Examples of bladder cancer include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma and small cell carcinoma. Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma Examples of liver cancers include, but are not limited to, hepatocellular carcinoma (liver cell carcinomas with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma. Example of skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non- melanoma skin cancer. Example of head-and-neck cancers include, but are not limited to, squamous cell cancer of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer and squamous cell. Example of lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system. Example of sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma. Example of leukemias include, but are not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. The eEF1A2 degraders/disruptors should be able to treat the above cancer type as stand alone agent or used as agent in combination with existing standard of treatment therapy and other FDA-approved cancer therapy. Therapeutic uses of eEF1A2 include diseases and therapies that are amenable to treatment by stimulation/augmentation of immune response, including the prolongation of immune responses during vaccination for immunizable diseases. Also, because eEF1A2 is expressed at high level in other anatomical locations – such as testes – the eEF1A2 degraders/disruptors should be able to treat or prevent diseases related to testes that were caused by eEF1A2 or could be treated by eEF1A2 degraders/disruptors. Successful strategies for selective degradation/disruption of the target protein induced by a bifunctional molecule include recruiting an E3 ubiquitin ligase and mimicking protein misfolding with a hydrophobic tag ^[23]. PROTACs (PROteolysis TArgeting Chimeras) are bivalent molecules with one moiety that binds an E3 ubiquitin ligase and another moiety that binds the protein target of interest ^[23]. The induced proximity leads to selective ubiquitination of the target followed by its degradation at the proteasome. Several types of high affinity small-molecule E3 ligase ligands have been identified/developed: They include (1) immunomodulatory drugs (IMiDs) such as thalidomide and pomalidomide, which bind cereblon (CRBN or CRL4^CRBN), a component of a cullin-RING ubiquitin ligase (CRL) complex ^{[20, 24]}; (2) VHL-1, a hydroxyproline-containing ligand, which binds van Hippel-Lindau protein (VHL or CRL2^VHL), a component of another CRL complex ^{[20, 25]}; (3) compound 7,which selectively binds KEAPl, a component of a CRL3 complex (Davies et al., 2016); (4) AMG232, which selectively binds MDM2, a heterodimeric RING E3 ligase (Sun et al., 2014); and (5) LCL161, which selectively binds IAP, a homodimeric RING E3 ligase (Ohoka et al., 2017; Okuhira et al, 2011; Shibata et al., 2017). The degrader technology has been successfully applied to degradation of multiple targets ^{[20, 24d, 25d, 26]}, but not to degradation of eEF1A2. In addition, a hydrophobic tagging approach, which utilizes a bulky and hydrophobic adamantyl group, has been developed to mimic protein misfolding, leading to the degradation of the target protein by proteasome ^[23]. This approach has also been successfully applied to selective degradation of the pseudokinase Her3 ^[27], but not to degradation of eEF1A2 proteins. As discussed in the following examples, this disclosure provides specific examples of novel eEF1A2 degraders/disruptors, and examined the effect of exemplary degraders/disruptors on reducing eEF1A2 protein levels, inhibiting/disrupting eEF1A2 activity and increasing the TCR-induced IL-2 production by Jurkat T cells. The results indicated that these novel compounds can be beneficial in treating cancer. Exemplary type of cancers that could be prevented, or therapeutically treated by manipulation of eEF1A2 level by degraders/disruptors should include all solid and liquid cancers, including, but not limited to, cancers of the breast, respiratory tract, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Examples of liquid cancers include lymphomas, sarcomas, and leukemias. Listed below are the type of cancers that immunotherapy using eEF1A2 degraders/disruptors should be able to prevent or treat as mentioned above. Current compounds targeting eEF1A2 generally focus on inhibition of its catalytic activity. In the present disclosure a different approach was taken: to develop compounds that directly and selectively target not only the catalytic function of eEF1A2, but also its protein level in cells. Strategies for inducing protein degradation include recruiting E3 ubiquitin ligases, mimicking protein misfolding with hydrophobic tags, and inhibiting chaperones. For example, a thalidomide-JQ1 bivalent compound has been used to hijack the cereblon E3 ligase, inducing highly selective BET protein degradation in vitro and in vivo and resulting in a demonstrated delay in leukemia progression in mice ^[24d]. Similarly, BET protein degradation has also been induced via another E3 ligase, VHL ^[25d]. Partial degradation of the Her3 protein has been induced using an adamantane-modified compound ^[27]. Such an approach, based on the use of bivalent molecules, permits more flexible regulation of protein levels in vitro and in vivo compared with techniques such as gene knockout or knockdown via RNA interference. Unlike gene knockout or knockdown, this chemical approach provides an opportunity to study dose and time dependency in a disease model by varying the concentrations and frequencies of administration of the relevant compound. This disclosure includes all stereoisomers, geometric isomers, tautomers and isotopes of the structures depicted and compounds named herein. This disclosure also includes compounds described herein, regardless of how they are prepared, e.g., synthetically, through biological process (e.g., metabolism or enzyme conversion), or a combination thereof. This disclosure includes pharmaceutically acceptable salts of the structures depicted and compounds named herein. One or more constituent atoms of the compounds presented herein can be replaced or substituted with isotopes of the atoms in natural or non-natural abundance. In some embodiments, the compound includes at least one deuterium atom in some embodiments, the compound includes two or more deuterium atoms. In some embodiments, the compound includes 1-2, 1-3, 1-4, 1-5, or 1-6 deuterium atoms. In some embodiments, all of the hydrogen atoms m a compound can be replaced or substituted by deuterium atoms. In some embodiments, the compound includes at least one fluorine atom ^{in some} embodiments, the compound includes two or more fluorine atoms. In some embodiments, the compound includes 1-2, 1-3, 1-4, 1-5, or 1-6 fluorine atoms. In some embodiments, all of the hydrogen atoms in a compound can be replaced or substituted by fluorine atoms. Degraders In some aspects, the present disclosure provides bivalent compounds, also referred to herein as degraders, comprising an eEF1A2 ligand (or targeting moiety) conjugated to a degradation tag. Linkage of the eEF1A2 ligand to the degradation tag can be direct, or indirect via a linker. As used herein, the terms “eukaryotic elongation factor 1 alpha 2 (eEF1A2) ligand” or “eEF1A2 ligand” or “eEF1A2 targeting moiety” are to be construed broadly, and encompass a wide variety of molecules ranging from small molecules to large proteins that associate with or bind to eEF1A2. The eEF1A2 ligand or targeting moiety can be, for example, a small molecule compound (i.e., a molecule of molecular weight less than about 15 kilodaltons (kDa)) a peptide or polypeptide nucleic acid or oligonucleotide, carbohydrate such as oligosaccharides, or an antibody or fragment thereof. The eEF1A2 ligand or targeting moiety can be derived from an eEF1A2 inhibitor (e.g., sutent and analogs thereof), which is capable of interfering with the enzymatic activity of eEF1A2. As used herein, an “inhibitor” refers to an agent that restrains, retards, or otherwise causes inhibition of a physiological, chemical or enzymatic action or function. As used herein an inhibitor causes a decrease in enzyme activity of at least 5%. An inhibitor can also or alternatively refer to a drug, compound, or agent that prevents or reduces the expression, transcription, or translation of a gene or protein. An inhibitor can reduce or prevent the function of a protein, e.g., by binding to or activating/inactivating another protein or receptor. Exemplary eEF1A2 ligands include, but are not limited to, the compounds listed below: As used herein, the term “degradation/disruption tag” refers to a compound, which associates with or binds to a ubiquitin ligase for recruitment of the corresponding ubiquitination machinery to eEF1A2 or induces eEF1A2 protein misfolding and subsequent degradation at the proteasome or loss of function. In some aspects, the degradation/disruption tags of the present disclosure include, e.g., thalidomide, pomalidomide, lenalidomide, VHL-1, adamantane, 1- ((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonane, nutlin-3a, RG7112, RG7338, AMG232, AA-115, bestatin, MV-1, LCL161, and/or analogs thereof. As used herein, a “linker” is a bond, molecule, or group of molecules that binds two separate entities to one another. Linkers can provide for optimal spacing of the two entities. The term “linker” in some aspects refers to any agent or molecule that bridges the eEF1A2 ligand to the degradation/disruption tag. One of ordinary skill in the art recognizes that sites on the eEF1A2 ligand or the degradation/disruption tag, which are not necessary for the function of the degraders of the present disclosure, are ideal sites for attaching a linker, provided that the linker, once attached to the conjugate of the present disclosure, does not interfere with the function of the degrader, i.e., its ability to target eEF1A2 and its ability to recruit a ubiquitin ligase. The length of the linker of the bivalent compound can be adjusted to minimize the molecular weight of the disruptors/degraders and avoid any potential clash of the eEF1A2 ligand or targeting moiety with either the ubiquitin ligase or the induction of eEF1A2 misfolding by the hydrophobic tag at the same time. In some aspects, the degradation/disruption tags of the present disclosure include, for example, thalidomide, pomalidomide, lenalidomide, VHL-1, adamantane, 1-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonane, nutlin-3a, RG7112, RG7338, AMG 232, AA-115, bestatin, MV-1, LCL161, and analogs thereof. The degradation/disruption tags can be attached to any portion of the structure of an eEF1A2 ligand or targeting moiety (e.g., sunitinib malate) with linkers of different types and lengths in order to generate effective bivalent compounds. In particular, attaching VHL1, pomalidomide, or LCL161 to any portion of the molecule can recruit the E3 ligase to eEF1A2. Additional bivalent compounds (i.e., eEF1A2 degraders/disruptors) can be developed using the principles and methods disclosed herein. For example, other linkers, degradation tags, and eEF1A2 binding/inhibiting moieties can be synthesized and tested. Non-limiting examples of eEF1A2 disruptors/degraders (e.g., bivalent compounds) are shown in Table 1 (below). The left portion of each eEF1A2 disruptors/degrader compound as shown binds to eEF1A2 (as sutent (sunitinib) do), and the right portion of each compound recruits for the ubiquitination machinery to eEF1A2, which induces the poly-ubiquitination and degradation of eEF1A2 at the proteasome. More specifically, the present disclosure provides a bivalent compound including an eEF1A2 ligand conjugated to a degradation/disruption tag. In some aspects, the eEF1A2 degraders/disruptors have the form “PI-linker- EL”, as shown below: PI Linker EL

wherein PI (protein of interest) comprises an eEF1A2 ligand (e.g., an eEF1A2 inhibitor) and EL (E3 ligase) comprises a degradation/disruption tag (e.g., E3 ligase ligand). Exemplary eEF1A2 ligands (PI), exemplary degradation/disruption tags (EL), and exemplary linkers (Linker) are illustrated below: eEF1A2 Ligands In one refinement, eEF1A2 ligands (PI) comprise a moiety of FORMULA 1:

FORMULA 1 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S In an embodiment, R¹ is selected from the following:

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰ , at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)2R¹¹, S(O)2NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)2R¹¹, NR¹³S(O)2NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1- C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Wherein; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1- C8 alkylaminoC1- C8 alkyl, optionally substituted C₃-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C8 cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH- CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 2:

FORMULA 2 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH- CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 3:

FORMULA 3 5 wherein, the “Linker” moiety of the bivalent compound is attached to N as indicated by the dotted line; X is selected from NH or O or S; Z is selected from N or CH The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C3- C13 fused heterocyclyl optionally substituted C₃-C₁₃ bridged cycloalkyl optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 4:

FORMULA 4 wherein, the “Linker” moiety of the bivalent compound is attached to N as indicated by the dotted line; X is selected from NH or O or S; Z is selected from N or CH The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH CH₂-NH-CH₂-NH-CO -CO-NH CO-NH- CH₂-NH-CH₂ CH₂-NH-CH₂ CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 5:^[KH2][RCSJ3]

FORMULA 5 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; The definitions of R1, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹⁷, R¹⁸, R¹⁹, R²⁰ are the same as for FORMULA 1 m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃- C13 fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 6: Ph Ph HN

FORMULA 6 wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH-CH₂-CO- NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁- C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. In an embodiment, (eEF1A2) ligands include a moiety according to FORMULA 6A and FORMULA 6B: Ph Ph

FORMULA 6A 10 Ph Ph HN H

FORMULA 6B ¹⁵ wherein, the “Linker” moiety of the bivalent compound is attached to Z as indicated by the dotted line; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH-CH₂-CO-²⁰ NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C3-C13 fused cycloalkyl, optionally substituted C3-C13 fused heterocyclyl optionally substituted C3-C13 bridged cycloalkyl optionally substituted C3-C13 bridged heterocyclyl, optionally substituted C3-C13 spiro cycloalkyl, and optionally substituted C3-C13 spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C1- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. Degradation/Disruption Tags Degradation/Disruption tags (EL) include, but are not limited to: In an embodiment, degradation/disruption tags include a moiety according to FORMULAE 12A, 12B, 12C and 12D: 1

FORMULA 12A FORMULA 12B FORMULA 12C FORMULA 12D, wherein V, W, and X are independently selected from CR² and N; Y is selected from CO, CR³R⁴, and N=N; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C₁-C₁₀ alkylene, optionally substituted C₁-C₁₀ alkenylene, optionally substituted C₁-C₁₀ alkynylene, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C3-C13 fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferly, Z is selected from null, CH₂, CH=CH, C≡ C, NH and O; R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl. In an embodiment, degradation/disruption tags include a moiety according to one of FORMULAE 12E, 12F, 12G, 12H, and 12I:

FORMULA 12E FORMULA 12F FORMULA 12G

FORMULA 12H FORMULA 12I wherein U, V, W, and X are independently selected from CR² and N; Y is selected from CR³R⁴, NR³ and O; preferably, Y is selected from CH₂, NH, NCH₃ and O; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C₁-C₁₀ alkylene, optionally substituted C₁-C₁₀ alkenylene, optionally substituted C₁-C₁₀ alkynylene, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferably, Z is selected from null, CH₂, CH=CH, C≡ C, NH and O; R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and pharmaceutically acceptable salts thereof.

In an embodiment, degradation/disruption tags include a moiety according to FORMULA 13A:

5 FORMULA 13A, wherein R¹ and R² are independently selected from hydrogen, optionally substituted C₁- C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; and R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O) C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)C₃- C₇ cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl, optionally substituted C(O)OC₁-C₈ hydroxyalkyl, optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C₇ cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC1- C8alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC1- C8 hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)N C₃-C₇ cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)2, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)₂. In an embodiment, degradation/disruption tags include a moiety according to FORMULAE 13B, 13C, 13D, 13E and 13F: 10

O U 3 O U 3C

wherein R¹ and R² are independently selected from hydrogen, halogen, OH, NH₂, CN, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC1- C₈alkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; (preferably, R¹ is selected from iso-propyl or tert-butyl; and R² is selected from hydrogen or methyl); R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl optionally substituted C(O)C₃- C7 cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl, optionally substituted C(O)OC₁-C₈ hydroxyalkyl, optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C7 cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC1- C8alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC1- C₈ hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)NC₃-C7 cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)2, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)2; and R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO₂R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁- C8alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁴ and R⁵; R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; Ar is selected from aryl and heteroaryl, each of which is optionally substituted with one or more substituents independently selected from F Cl CN NO2 OR⁸ NR⁸R⁹, COR⁸, CO2R⁸, CONR⁸R⁹, SOR⁸, SO2R⁸, SO2NR⁹R¹⁰, NR⁹COR¹⁰, NR⁸C(O)NR⁹R¹⁰, NR⁹SOR¹⁰, NR⁹SO2R¹⁰, optionally substituted C₁-C₆ alkyl, optionally substituted C1-C6 alkoxyalkyl, optionally substituted C₁-C₆ haloalkyl, optionally substituted C₁-C₆ hydroxyalkyl, optionally substituted C₁-C₆alkylaminoC₁- C₆alkyl, optionally substituted C_3-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₆ alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted aryl, and optionally substituted C4-C5 heteroaryl; wherein R⁸, R⁹, and R¹⁰ are independently selected from null, hydrogen, optionally substituted C₁-C₆ alkyl, optionally substituted C_2-C₆ alkenyl, optionally substituted C₂- C₆ alkynyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁸ and R⁹; R⁹ and R¹⁰ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; and pharmaceutically acceptable salts thereof. In an embodiment, degradation/disruption tags include a moiety according to FORMULA 14A:

FORMULA 14A, wherein V, W, X, and Z are independently selected from CR⁴ and N; R¹, R², R³, and R⁴ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl. In an embodiment, degradation/disruption tags include a moiety according to FORMULA 14B: 5

FORMULA 14B, wherein R¹, R², and R³ are independently selected from hydrogen, halogene, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO₂R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted aryl-C₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C1- C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; and pharmaceutically acceptable salts thereof In an embodiment, degradation/disruption tags are selected from the group consisting of:

;

and pharmaceutically acceptable salts thereof. LINKERS In any of the above-described compounds, the eEF1A2 ligand can be conjugated to the degradation/disruption tag through a linker. The linker can include, e.g., acyclic or cyclic saturated or unsaturated carbon, ethylene glycol, amide, amino, ether, urea, carbamate, aromatic, heteroaromatic, heterocyclic, and/or carbonyl containing groups with different lengths. In an embodiment, the linker is a moiety according to FORMULA 16: 10

FORMULA 16, wherein A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR¹, C(S)NR¹, O, S, SO, SO₂, SO₂NR¹, NR¹, NR¹CO, NR¹CONR²,15 NR¹C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy,optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R¹ and R² are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted 3-8 membered cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy optionally substituted C₁-C₈ alkoxyalkyl optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; and m is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16A:

FORMULA 16A, wherein R¹, R², R³, and R⁴, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR⁵, C(S)NR⁵, O, S, SO, SO₂, SO₂NR⁵, NR⁵, NR⁵CO, NR⁵CONR⁶, NR⁵C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged C3-C13 spiro heterocyclyl; wherein R⁵ and R⁶ are independently selected from hydrogen, optionally substituted C₁- C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; m is 0 to 15; n, at each occurrence, is 0 to 15; o is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16B:

wherein R¹ and R², at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH2, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C1- C8alkylaminoC₁-C₈alkyl; A and B, at each occurrence, are independently selected from null, CO, CO₂, C(O)NR³, C(S)NR³, O, S, SO, SO2, SO2NR³, NR³, NR³CO, NR³CONR⁴, NR³C(S), and optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃- C13 fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, or C₃-C₁₃ spiro heterocyclyl; wherein R³ and R⁴ are independently selected from hydrogen, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃- C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C₁-C₈alkylaminoC₁-C₈alkyl; each m is 0 to 15; and n is 0 to 15. In an embodiment, the linker is a moiety according to FORMULA 16C:

FORMULA 16C, wherein X is selected from O, NH, and NR⁷; R¹, R², R³, R⁴, R⁵, and R⁶, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A and B, at each occurrence, are independently selected from null, CO, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CO2, C(O)NR⁷, C(S)NR⁷, O, S, SO, SO₂, SO₂NR⁷, NR⁷, NR⁷CO, NR⁷CONR⁸, NR⁷C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R⁷ and R⁸ are independently selected from hydrogen, optionally substituted C₁- C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; m, at each occurrence, is 0 to 15; n at each occurrence is 0 to 15; o is 0 to 15; and p is 0 to 15; and pharmaceutically acceptable salts thereof. In an embodiment, the linker is selected from the group consisting of a ring selected from the group consisting of a 3 to 13 membered ring; a 3 to 13 membered fused ring; a 3 to 13 membered bridged ring; and a 3 to13 membered spiro ring; and pharmaceutically acceptable salts thereof. In an embodiment, the linker is a moiety according to one of FORMULAE C1, C2, C3, C4 and C5: FORMULA C1, FORMULA C2, FORMULA C₃,

FORMULA C4, and

FORMULA C5; and

pharmaceutically acceptable salts thereof. In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS106-033, NS106-034, NS106-035, NS106-036, NS106-037, NS106-038, NS106-039, NS106-084, NS106-085, NS106-086, NS106- 087, NS106-088, NS113-167, NS106-094, NS106-040, NS106-041, NS106-042, NS106-043, NS106-044, NS106-045, NS106-046, NS106-047, NS106-048, NS106- 049, NS113-044, NS113-045, NS113-046, NS113-047, NS113-048, NS113-049, NS113-050, NS113-051, NS113-052, NS113-053, NS113-054, NS113-055, NS113- 056, NS113-057, NS113-058, NS113-059, NS113-060 and NS113-061; and pharmaceutically acceptable salts thereof. In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS106-051, NS106-052, NS106-053, NS106-054, NS106-055, NS106-056, NS106-057, NS106-058, NS106-059, NS106-060, NS106- 061, NS106-078, NS106-079, NS106-096, NS106-080, NS106-081, NS106-082, NS106-083, NS106-111, NS113-168, NS106-065, NS106-066, NS106-067, NS106- 068, NS106-069, NS106-070,, NS106-071, NS106-072, NS106-073, NS106-074, NS113-093, NS106-075, NS113-094, NS106-076, NS113-095, NS113-096, NS106- 077, NS113-028, NS113-029, NS113-030, NS113-031, NS113-032, NS113-033, NS113-034, NS113-083, NS113-084, NS113-085, NS113-086, NS113-087, NS113- 039, NS113-040, NS113-041, NS113-042, NS113-043, NS113-088, NS113-089, NS113-090, NS113-091 and NS113-092; and pharmaceutically acceptable salts thereof. In an embodiment, the bivalent compound according to the present invention is selected from the group consisting of: NS113-075, NS113-076, NS113-077, NS113-078, NS113-079, NS113-080, NS113-081 and NS113-082; and pharmaceutically acceptable salts thereof. In one embodiment, preferred compounds according to the present invention include: a. N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N9-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)nonanediamide (NS106-070). b. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((6-((6-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)amino)-6-oxohexyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-043). c. (2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-((S)-3-((12-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamido)dodecyl)amino)-1-(4-(4-methylthiazol-5- yl)phenyl)-3-oxopropyl)pyrrolidine-2-carboxamide (NS113-054). d. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((2-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)ethyl)amino)-2-oxoethoxy)- 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-055). e. (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((3-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)propyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-056). f. (2S,4R)-1-((S)-2-(tert-butyl)-21-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)-4,14-dioxo-6,9,12-trioxa-3,15-diazahenicos-20-ynoyl)-4- hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-094). g. N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N17-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12,15- pentaoxaheptadecanediamide (NS113-096). In one embodiment, preferred compounds according to the present invention include: a. 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS106-078). b. 3-(4-(5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[23-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)amino)pent-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (NS113- 168). In one embodiment, preferred compounds according to the present invention include: a. (3r,5r,7r)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)adamantane-1-carboxamide (NS121-135). b. 2-((3r,5r,7r)-adamantan-1-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS121-136). In some aspects, this disclosure provides a method of treating the eEF1A2- mediated diseases, the method including administering to a subject in need thereof with an eEF1A2-mediated disease one or more bivalent compounds including an eEF1A2 ligand conjugated to a degradation/disruption tag. The eEF1A2-mediated diseases may be a disease resulting from eEF1A2 amplification. The eEF1A2- mediated diseases can have elevated eEF1A2 activity relative to a wild-type tissue of the same species and tissue type. Non-limiting examples of eEF1A2-mediated diseases or diseases whose clinical symptoms could be treated by eEF1A2 degraders/disruptors-mediated therapy include: all solid and liquid cancer, chronic infections that produce exhausted immune response, infection-mediated immune suppression, age-related decline in immune response, age-related decline in cognitive function and infertility. Exemplary types of cancer that could prevented, or therapeutically treated by manipulation of eEF1A2 level by degraders/disruptors should include all solid and liquid cancers, including, but not limited to, cancers of the breast, respiratory tract, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid parathyroid and their distant metastases Examples of liquid cancers include lymphomas, sarcomas, and leukemias. Listed below are the type of cancers that immunotherapy using eEF1A2 degraders/disruptors should be able to prevent or treat. Examples of breast cancers include, but are not limited to, triple negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ. Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non- small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma. Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer. Tumors of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus. Examples of ovarian cancer include, but are not limited to, serous tumor, endometrioid tumor, mucinous cystadenocarcinoma, granulosa cell tumor, Sertoli- Leydig cell tumor and arrhenoblastoma. Examples of cervical cancer include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumor, glassy cell carcinoma and villoglandular adenocarcinoma. Tumors of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancers. Examples of esophageal cancer include, but are not limited to, esophageal cell carcinomas and adenocarcinomas, as well as squamous cell carcinomas, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma and lymphoma. Examples of gastric cancer include, but are not limited to, intestinal type and diffuse type gastric adenocarcinoma. Examples of pancreatic cancer include, but are not limited to, ductal adenocarcinoma adenosquamous carcinomas and pancreatic endocrine tumors Example of tumors of the urinary tract include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral and human papillary renal cancers. Examples of kidney cancer include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (reninoma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear-cell sarcoma of the kidney, mesoblastic nephroma and Wilms' tumor. Examples of bladder cancer include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma and small cell carcinoma. Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma. Examples of liver cancers include, but are not limited to, hepatocellular carcinoma (liver cell carcinomas with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma. Example of skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non- melanoma skin cancer. Example of head-and-neck cancers include, but are not limited to, squamous cell cancer of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer and squamous cell. Example of lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system. Example of sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma. Example of leukemias include, but are not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. The eEF1A2 degraders/disruptors should be able to treat the above cancer types as stand alone agents or used as an agent in combination with existing standards of treatment therapy and other FDA-approved cancer therapy. Therapeutic use of eEF1A2 extends to include diseases and therapies that are amenable to treatment by stimulation/augmentation of immune response, including the prolongation of immune responses during vaccination for immunizable diseases such as influenza and coronaviruses, including Covid 19. Also, because eEF1A2 is expressed at high level in other anatomical locations – such as testes – the eEF1A2 degraders/disruptors should be able to treat or prevent diseases related to testes that were caused by eEF1A2 or could be treated by eEF1A2 degraders/disruptors. Therapeutic use of eEF1A2 further extends to include therapies involving ex vivo treatment of immune cells, including, but not limited to, all T cell subsets, genetically engineered T cells, Chimeric Antigen Receptor (CAR) T cells, tumor infiltrating lymphocytes, dendritic cells, macrophage, mast cells, granulocytes (include basophils, eosinophils, and neutrophils), natural killer cells, NK T cells and B cells. Such cells would be therapeutically treated by eEF1A2 degraders and then re- introduced back to the patient being treated for conditions that would benefit from reduction in eEF1A2 expression. The sources of cells for such ex vivo treatment include, but are not limited to, the autologous bone marrow cells from the patient him/herself, or from the patient’s frozen banked cord blood stem cells, peripheral blood or bone marrow stem cells from MHC-matched or MHC-mismatched donors. Treating patients by administering specific immune cells that had been treated with eEF1A2 degraders offers many added advantages over in vivo use. By treating specific immune cells type with eEF1A2 degraders ex vivo, it is possible to specifically target the immune cell type that would receive the benefit of having the endogenous eEF1A2 level reduced by eEF1A2 degraders while sparing the eEF1A2 expression level in other immune cell types that are not involved in the disease condition. This therapeutic approach would provide cell type-specific targeting of immune cells in a way that is not possible with the use of eEF1A2 degrader in the in vivo setting. Thus, the ex vivo approach would likely limit potential toxicity that may result from reduction of HPK1 level in immune cell types that do not benefit from a reduction in eEF1A2 levels. Furthermore, by administering eEF1A2 degraders in the ex vivo cell setting, the risk of patients experiencing the toxicity or undesirable outcome that might occur should the eEF1A2 degraders were to be administered systemically would be eliminated. It is known that eEF1A2 is also expressed in non-hematopoietically-derived tissues such as the testes. Because of this tissue-specific expression pattern of eEF1A2, eEF1A2 degraders might be able to treat or prevent diseases related to the testes that were caused by eEF1A2. The use of eEF1A2 expression status of the tumor as the biomarker would enable stratification of patients into appropriate therapeutic groups that would receive eEF1A2 degraders in vivo or ex vivo, based on eEF1A2 expression in the tumors. Furthermore, using eEF1A2 degraders in an ex vivo setting offers additional advantages over gene-editing approaches such as CRISPR in that it allows therapeutic use of eEF1A2 degraders as a non-permanent treatment that allows a therapeutic regimen to be adjusted temporally through dosing levels and through alteration of the administration schedule. In addition, eEF1A2 degraders could be used in settings whereby stimulation/augmentation of the immune response is required, or when the prolongation of immune responses is needed. Improving immune response to vaccination is one of the settings in which eEF1A2 degraders could be used therapeutically. eEF1A2 degraders could also be used to enhance the antigen presentation capability of dendritic cell-based cancer vaccines Other utilities of eEF1A2 degraders include treatment of dendritic cells with eEF1A2 degraders to increase resistance to maturation-induced apoptosis, thus increasing the yield of dendritic cell production. In any of the above-described methods, the bivalent compounds can be NS106-033, NS106-034, NS106-035, NS106-036, NS106-037, NS106-038, NS106-039, NS106- 084, NS106-085, NS106-086, NS106-087, NS106-088, NS113-167, NS106-094, NS106-040, NS106-041, NS106-042, NS106-043, NS106-044, NS106-045, NS106- 046, NS106-047, NS106-048, NS106-049, NS113-044, NS113-045, NS113-046, NS113-047, NS113-048, NS113-049, NS113-050, NS113-051, NS113-052, NS113- 053, NS113-054, NS113-055, NS113-056, NS113-057, NS113-058, NS113-059, NS113-060, NS113-061, NS106-051, NS106-052, NS106-053, NS106-054, NS106- 055, NS106-056, NS106-057, NS106-058, NS106-059, NS106-060, NS106-061, NS106-078, NS106-079, NS106-096, NS106-080, NS106-081, NS106-082, NS106- 083, NS106-111, NS113-168, NS106-065, NS106-066, NS106-067, NS106-068, NS106-069, NS106-070, NS106-071, NS106-072, NS106-073, NS106-074, NS113- 093, NS106-075, NS113-094, NS106-076, NS113-095, NS113-096, NS106-077, NS113-028, NS113-029, NS113-030, NS113-031, NS113-032, NS113-033, NS113- 034, NS113-083, NS113-084, NS113-085, NS113-086, NS113-087, NS113-039, NS113-040, NS113-041, NS113-042, NS113-043, NS113-088, NS113-089, NS113- 090, NS113-091, NS113-092, NS113-075, NS113-076, NS113-077, NS113-078, NS113-079, NS113-080, NS113-081, NS113-082, NS121-135, NS121-136, NS121- 137, NS121-138, NS121-139, NS121-140, NS121-141, NS121-142 or analogs thereof. In some aspects of the disclosed methods, the bivalent compounds can be administered by any of several routes of administration including, e.g., orally, parenterally, intradermally, subcutaneously, topically, and/or rectally. Any of the above-described methods can further include treating the subject with one or more additional therapeutic regimens for treating cancer. The one or more additional therapeutic regimens for treating cancer can be, e.g., one or more of surgery, chemotherapy, radiation therapy, hormone therapy, or immunotherapy. This disclosure additionally provides a method for identifying a bivalent compound which mediates degradation/disruption of eEF1A2, the method including providing a heterobifunctional test compound including an eEF1A2 ligand conjugated to a degradation/disruption tag, contacting the heterobifunctional test compound with a cell (e.g., a cancer cell such as an eEF1A2-mediated cancer cell) including a ubiquitin ligase and eEF1A2. Pharmaceutical Compositions In some aspects, the compositions and methods described herein include the manufacture and use of pharmaceutical compositions and medicaments that include one or more bivalent compounds as disclosed herein. Also included are the pharmaceutical compositions themselves. In some aspects, the compositions disclosed herein can include other compounds, drugs, or agents used for the treatment of cancer. For example, in some instances, pharmaceutical compositions disclosed herein can be combined with one or more (e.g., one, two, three, four, five, or less than ten) compounds. Such additional compounds can include, for example, conventional chemotherapeutic agents known in the art. When co-administered, eEF1A2 degraders/disruptors disclosed herein can operate in conjunction with conventional chemotherapeutic agents to produce mechanistically additive or synergistic therapeutic effects. In some aspects, the pH of the compositions disclosed herein can be adjusted with pharmaceutically acceptable acids, bases, or buffers to enhance the stability of the degraders/disruptor or its delivery form. Pharmaceutical compositions typically include a pharmaceutically acceptable carrier, adjuvant, or vehicle. As used herein, the phrase “pharmaceutically acceptable” refers to molecular entities and compositions that are generally believed to be physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, when administered to a human. A pharmaceutically acceptable carrier, adjuvant, or vehicle is a composition that can be administered to a patient, together with a compound of the invention, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the compound. Exemplary conventional nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles include saline, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. In particular, pharmaceutically acceptable carriers, adjuvants, and vehicles that can be used in the pharmaceutical compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d-!-tocopherol polyethylene glycol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tweens or other similar polymeric delivery matrices, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Cyclodextrins such as !-, "-, and #- cyclodextrin, may also be advantageously used to enhance delivery of compounds of the formulae described herein As used herein, the present degraders/disruptors disclosed herein are defined to include pharmaceutically acceptable derivatives or prodrugs thereof. A “pharmaceutically acceptable derivative” means any pharmaceutically acceptable salt, solvate, or prodrug, e.g., carbamate, ester, phosphate ester, salt of an ester, or other derivative of a compound or agent disclosed herein, which upon administration to a recipient is capable of providing (directly or indirectly) a compound described herein, or an active metabolite or residue thereof. Particularly favored derivatives and prodrugs are those that increase the bioavailability of the compounds disclosed herein when such compounds are administered to a mammal (e.g., by allowing an orally administered compound to be more readily absorbed into the blood) or which enhance delivery of the parent compound to a biological compartment (e.g., the lymphatic system) relative to the parent species. Preferred prodrugs include derivatives where a group that enhances aqueous solubility or active transport through the gut membrane is appended to the structure of formulae described herein. Such derivatives are recognizable to those skilled in the art without undue experimentation. Nevertheless, reference is made to the teaching of Burger's Medicinal Chemistry and Drug Discovery, 5th Edition, Vol. 1: Principles and Practice, which is incorporated herein by reference to the extent of teaching such derivatives. The degraders/disruptors disclosed herein include pure enantiomers, mixtures of enantiomers, pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates, mixtures of diastereoisomeric racemates and the meso-form and pharmaceutically acceptable salts, solvent complexes, morphological forms, or deuterated derivative thereof. In particular, pharmaceutically acceptable salts of the degraders/disruptors disclosed herein include, for example, those derived from pharmaceutically acceptable inorganic and organic acids and bases Examples of suitable acid salts include acetate adipate, benzoate, benzenesulfonate, butyrate, citrate, digluconate, dodecylsulfate, formate, fumarate, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, palmoate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, tartrate, tosylate, trifluoromethylsulfonate, and undecanoate. Salts derived from appropriate bases include, for example, alkali metal (e.g., sodium), alkaline earth metal (e.g., magnesium), ammonium and N- (alkyl)4+ salts. The invention also envisions the quaternization of any basic nitrogen- containing groups of the degraders/disruptors disclosed herein. Water or oil-soluble or dispersible products can be obtained by such quaternization. In some aspects, the pharmaceutical compositions disclosed herein can include an effective amount of one or more degraders/disruptors. The terms “effective amount” and “effective to treat,” as used herein, refer to an amount or a concentration of one or more compounds or a pharmaceutical composition described herein utilized for a period of time (including acute or chronic administration and periodic or continuous administration) that is effective within the context of its administration for causing an intended effect or physiological outcome (e.g., treatment or prevention of cell growth, cell proliferation, or cancer). In some aspects, pharmaceutical compositions can further include one or more additional compounds, drugs, or agents used for the treatment of cancer (e.g., conventional chemotherapeutic agents) in amounts effective for causing an intended effect or physiological outcome (e.g., treatment or prevention of cell growth, cell proliferation, or cancer). In some aspects, the pharmaceutical compositions disclosed herein can be formulated for sale in the United States, import into the United States, or export from the United States. Administration of Pharmaceutical Compositions The pharmaceutical compositions disclosed herein can be formulated or adapted for administration to a subject via any route, for example, any route approved by the Food and Drug Administration (FDA). Exemplary methods are described in the FDA Data Standards Manual (DSM) (available at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirem ents/ElectronicSubmissions/DataStandardsManualmonographs). In particular, the pharmaceutical compositions can be formulated for and administered via oral, parenteral, or transdermal delivery. The term “parenteral” as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraperitoneal, intra- articular, intra-arterial, intrasynovial, intrasternal, intrathecal, intralesional, and intracranial injection or infusion techniques. For example, the pharmaceutical compositions disclosed herein can be administered, for example, topically, rectally, nasally (e.g., by inhalation spray or nebulizer), buccally, vaginally, subdermally (e.g., by injection or via an implanted reservoir), or ophthalmically. For example, pharmaceutical compositions of this invention can be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, emulsions and aqueous suspensions, dispersions and solutions. In the case of tablets for oral use, carriers which are commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions or emulsions are administered orally, the active ingredient may be suspended or dissolved in an oily phase is combined with emulsifying or suspending agents. If desired, certain sweetening, flavoring, or coloring agents can be added. For example, the pharmaceutical compositions of this invention can be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound of this invention with a suitable non-irritating excipient which is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components. Such materials include, but are not limited to, cocoa butter, beeswax, and polyethylene glycols. For example, the pharmaceutical compositions of this invention can be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and can be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, or other solubilizing or dispersing agents known in the art. For example, the pharmaceutical compositions of this invention can be administered by injection (e.g., as a solution or powder). Such compositions can be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non- toxic parenterally acceptable diluent or solvent, e.g., as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are mannitol, water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed, including synthetic mono- or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, e.g., olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions can also contain a long-chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents which are commonly used in the formulation of pharmaceutically acceptable dosage forms such as emulsions and or suspensions. Other commonly used surfactants such as Tweens, Spans, or other similar emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms can also be used for the purposes of formulation. In some aspects, an effective dose of a pharmaceutical composition of this invention can include, but is not limited to about 0.00001, 0.0001, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2500, 5000, or 10000 mg/kg/day, or according to the requirements of the particular pharmaceutical composition. When the pharmaceutical compositions disclosed herein include a combination of a compound of the formulae described herein (e.g., degraders/disruptors) and one or more additional compounds (e.g., one or more additional compounds, drugs, or agents used for the treatment of cancer or any other condition or disease, including conditions or diseases known to be associated with or caused by cancer), both the compound and the additional compound should be present at dosage levels of between about 1 to 100%, and more preferably between about 5 to 95% of the dosage normally administered in a monotherapy regimen. The additional agents can be administered separately, as part of a multiple dose regimen, from the compounds of this invention. Alternatively, those agents can be part of a single dosage form, mixed together with the compounds of this invention in a single composition. In some aspects, the pharmaceutical compositions disclosed herein can be included in a container, pack, or dispenser together with instructions for administration. Methods of Treatment The methods disclosed herein contemplate administration of an effective amount of a compound or composition to achieve the desired or stated effect. Typically, the compounds or compositions of the invention will be administered from about 1 to about 6 times per day or, alternately or in addition, as a continuous infusion. Such administration can be used as a chronic or acute therapy. The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. A typical preparation will contain from about 5% to about 95% active compound (w/w). Alternatively, such preparations can contain from about 20% to about 80% active compound. In some aspects, the present disclosure provides methods for using a composition comprising a degrader/disruptor, including pharmaceutical compositions (indicated below as ‘X’) disclosed herein in the following methods: Substance X for use as a medicament in the treatment of one or more diseases or conditions disclosed herein (e.g., cancer, referred to in the following examples as ‘Y’). Use of substance X for the manufacture of a medicament for the treatment of Y; and substance X for use in the treatment of Y. In some aspects, the methods disclosed include the administration of a therapeutically effective amount of one or more of the compounds or compositions described herein to a subject (e.g., a mammalian subject, e.g., a human subject) who is in need of, or who has been determined to be in need of, such treatment. In some aspects, the methods disclosed include selecting a subject and administering to the subject an effective amount of one or more of the compounds or compositions described herein, and optionally repeating administration as required for the prevention or treatment of cancer. In some aspects, subject selection can include obtaining a sample from a subject (e.g., a candidate subject) and testing the sample for an indication that the subject is suitable for selection. In some aspects, the subject can be confirmed or identified, e.g. by a health care professional, as having had or having a condition or disease. In some aspects, suitable subjects include, for example, subjects who have or had a condition or disease but that resolved the disease or an aspect thereof, present reduced symptoms of disease (e.g., relative to other subjects (e.g., the majority of subjects) with the same condition or disease), or that survive for extended periods of time with the condition or disease (e.g., relative to other subjects (e.g., the majority of subjects) with the same condition or disease), e.g., in an asymptomatic state (e.g., relative to other subjects (e.g., the majority of subjects) with the same condition or disease). In some aspects, exhibition of a positive immune response towards a condition or disease can be made from patient records, family history, or detecting an indication of a positive immune response. In some aspects, multiple parties can be included in subject selection. For example, a first party can obtain a sample from a candidate subject and a second party can test the sample. In some aspects, subjects can be selected or referred by a medical practitioner (e.g., a general practitioner). In some aspects, subject selection can include obtaining a sample from a selected subject and storing the sample or using the in the methods disclosed herein. Samples can include, e.g., cells or populations of cells. In some aspects, methods of treatment can include a single administration, multiple administrations, and repeating administration of one or more compounds disclosed herein as required for the prevention or treatment of the disease or condition from which the subject is suffering (e.g., an eEF1A2-mediated cancer). In some aspects, methods of treatment can include assessing a level of disease in the subject prior to treatment, during treatment, or after treatment. In some aspects, treatment can continue until a decrease in the level of disease in the subject is detected. The term “subject,” as used herein, refers to any animal. In some instances, the subject is a mammal. In some instances, the term “subject,” as used herein, refers to a human (e.g., a man, a woman, or a child). The terms “administer,” “administering,” or “administration,” as used herein, refer to implanting, ingesting, injecting, inhaling, or otherwise absorbing a compound or composition, regardless of form. For example, the methods disclosed herein include administration of an effective amount of a compound or composition to achieve the desired or stated effect. The terms “treat”, “treating,” or “treatment,” as used herein, refer to partially or completely alleviating, inhibiting, ameliorating, or relieving the disease or condition from which the subject is suffering. This means any manner in which one or more of the symptoms of a disease or disorder (e.g., cancer) are ameliorated or otherwise beneficially altered. As used herein, amelioration of the symptoms of a particular disorder (e.g., cancer) refers to any lessening, whether permanent or temporary, lasting or transient that can be attributed to or associated with treatment by the compositions and methods of the present invention. In some embodiments, treatment can promote or result in, for example, a decrease in the number of tumor cells (e.g., in a subject) relative to the number of tumor cells prior to treatment; a decrease in the viability (e.g., the average/mean viability) of tumor cells (e.g., in a subject) relative to the viability of tumor cells prior to treatment; a decrease in the rate of growth of tumor cells; a decrease in the rate of local or distant tumor metastasis; or reductions in one or more symptoms associated with one or more tumors in a subject relative to the subject's symptoms prior to treatment. As used herein, the term “treating cancer” means causing a partial or complete decrease in the rate of growth of a tumor, and/or in the size of the tumor and/or in the rate of local or distant tumor metastasis, and/or the overall tumor burden in a subject, and/or any decrease in tumor survival, in the presence of a degrader/disruptor as described herein. The terms “prevent,” “preventing,” and “prevention,” as used herein, shall refer to a decrease in the occurrence of a disease or decrease in the risk of acquiring a disease or its associated symptoms in a subject. The prevention may be complete, e.g., the total absence of disease or pathological cells in a subject. The prevention may also be partial, such that the occurrence of the disease or pathological cells in a subject is less than, occurs later than, or develops more slowly than that which would have occurred without the present invention. As used herein, the terms “about” and “approximately” are defined as being within plus or minus 10% of a given value or state, preferably within plus or minus 5% of said value or state. EXAMPLES The following Examples describe the synthesis of exemplary eEF1A2 degrader/disrupter compounds according to the present invention. Example 1 Synthesis of Intermediate 1 NS106-026

To a stirred solution of benzoin (2.1 g, 10 mmol), (3-bromophenyl)methanamine (3.3 g, 15 mmol, 1.5 equiv.), and trifluoroacetic acid (57 mg, 0.1 mmol, 0.05 equiv.) were heated at reflux for 1 h connected to a Dean-Stark trap, and the mixture was removed from the oil bath. Malononitrile (990.9 mg, 15 mmol, 1.5 equiv.) was added to the mixture, and the reaction heated at reflux for 1 h connected to a Dean-Stark trap. The reaction mixture was allowed to cool to room temperature and stirred for 1 h, affording the crude pyrrole as a dark brown solid. The product was further precipitated with ethyl ether and the solid washed with additional ethyl ether until the filtrate was colorless, affording the reported pyrrole product as a yellow solid (2.6 g, 61% yield) without further purification. 2-Amino-1-(3-bromobenzyl)-4,5-diphenyl-1H-pyrrole-3-carbonitrile (2.6 g, 6 mmol) and triethylorthoformate (8.9 g, 60 mmol, 10.0 equiv.) were heated at 65 °C for 18 h, and the excess triethylorthoformate was removed in vacuo. The residue was dissolved in a minimum of CH₂Cl₂, adsorbed onto celite, and chromatographed on silica (20% EtOAc in hexanes) to afford the reported formimidate product as a yellow solid (1.47 g, 51% yield). A solution of (E)-ethyl N-(1-(3-bromobenzyl)-3-cyano-45-diphenyl-1H-pyrrol-2- yl)formimidate (1.47 g, 3 mmol), trans-4-aminocyclohexanol hydrochloride (909.8 mg, 6 mmol, 2.0 equiv), and potassium tert-butoxide (1.009 g, 9 mmol, 3.0 equiv.) in MeOH (20 mL) was heated at 50 ºC for 19 h, and then cooled to room temperature and filtered. The precipitate was washed with MeOH (2 x 10 mL). The filtrate was purified by silica gel (10% MeOH in CH₂Cl₂) to afford the pyrrolopyrimidine product (1r,4r)-4-(7-(3- bromobenzyl)-4-imino-5,6-diphenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3- yl)cyclohexan-1-ol as a yellow solid (590 mg, 36% yield). ¹H NMR (800 MHz, Methanol-d4) δ 8.06 (s, 1H), 7.35 – 7.20 (m, 9H), 7.11 – 7.04 (m, 3H), 6.98 (s, 1H), 6.83 (d, J = 7.8 Hz, 1H), 5.31 (s, 2H), 3.69 (d, J = 4.3 Hz, 1H), 3.35 (s, 1H), 2.12 – 2.03 (m, 4H), 1.87 (d, J = 12.4 Hz, 2H), 1.57 – 1.52 (m, 2H).HRMS (ESI) m/z: calcd for C₃1H30BrN4O⁺ [M + H]⁺, 553.1598; found, 553.1530 To a solution of trans-4-(7-(3-Bromobenzyl)-4-imino-5,6-diphenyl-4,7-dihydro-3H- pyrrolo[2,3-d]pyrimidin-3-yl)cyclohexanol (162 mg, 0.29 mmol) and hept-6-ynoic acid (47.6 mg, 0.377 mmol, 1.3 equiv.) in triethylamine (1 mL) and DMF (2 mL), were added copper (I) iodide (11 mg, 0.058 mmol) and bis(triphenylphosphine)palladium(II) chloride (20.4 mg, 0.029 mmol). The flask was capped and the atmosphere evacuated and backfilled with nitrogen three times. The reaction was heated at 80 ºC for 12 h under nitrogen atmosphere. After cooling to room temperature (RT), the reaction was adsorbed onto Celite and immediately purified by reverse C18 column (eluent: with 10%-100% (v1:v2) acetonitrile in water (contain 0.1% trifluoroacetic acid)) to give the Intermediate 1 as a yellow solid (156.5 mg, 90% yield). ¹H NMR (800 MHz, Methanol-d4) δ 8.72 (s, 1H), 7.39 (d, J = 6.7 Hz, 3H), 7.33 (q, J = 7.4 Hz, 4H), 7.21 – 7.08 (m, 5H), 6.85 (s, 1H), 6.80 (d, J = 7.8 Hz, 1H), 5.46 (s, 2H), 4.44 (d, J = 12.3 Hz, 1H), 3.77 (d, J = 11.9 Hz, 1H), 2.40 (t, J = 7.0 Hz, 2H), 2.35 (t, J = 7.5 Hz, 2H), 2.21 – 2.10 (m, 6H), 1.75 (q, J = 7.7 Hz, 2H), 1.65-1.58 (m, 4H). HRMS (ESI) m/z: calcd for C₃8H39N4O3⁺ [M + H]⁺, 599.3017; found, 599.2973 Example 2 Synthesis of Intermediate 2 NS106-050

To a stirred solution of hex-5-yn-1-amine hydrogen chloride (504 mg, 3.8 mmol, 1.0 equiv.) in CH2Cl₂ (6 mL) were added Et3N (1.6 mL, 11.4 mmol, 3.0 equiv.) and (Boc)2O (1.244g, 5.7 mmol, 1.5 equiv.). Then the resulting mixture was stirred at room temperature for 2 h. When the reaction was complete, the crude mixture was quenched by saturated ammonium chloride solution, extracted by methylene chloride, dried by anhydrous sodium sulfate. The mixture was purified by silica gel (3% MeOH in CH2Cl2) to afford tert-butyl hex-5-yn-1-ylcarbamate as a transparent liquid (741 mg, 99% yield). To a solution of trans-4-(7-(3-Bromobenzyl)-4-imino-5,6-diphenyl-4,7-dihydro-3H- pyrrolo[2,3-d]pyrimidin-3-yl)cyclohexanol (166 mg, 0.3 mmol) and tert-butyl hex-5- yn-1-ylcarbamate (88.7 mg, 0.45 mmol, 1.5 equiv.) in triethylamine (1 mL) and DMF (2 mL), were added copper (I) iodide (11.4 mg, 0.06 mmol) and bis(triphenylphosphine)palladium(II) chloride (21.2 mg, 0.03 mmol). The flask was capped and the atmosphere evacuated and backfilled with nitrogen three times. The reaction was heated at 80 ºC for 12 h under nitrogen atmosphere. After cooling to room temperature (RT), the reaction was adsorbed onto Celite and immediately purified by reverse C18 column (eluent: with 10%-100% (v1:v2) methanol in water (contain 0.1% trifluoroacetic acid)) to give the tert-butyl (6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-0 5-yn-1-yl)carbamate as a yellow solid (185 mg, 92% yield). To a mixture of this tert- butyl carbamate, methanol (1 mL) and 4N HCl in dioxane (2 mL) was stirred at 25 ^oC for 1 h. When the reaction was complete, the crude mixture was evaporated under the reduced pressure, the residue was purified by freeze-drying to obtain target Intermediate 2 (1r,4r)-4-(7-(3-(6-aminohex-1-yn-1-yl)benzyl)-4-imino-5,6-diphenyl- 4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)cyclohexan-1-ol as a yellow solid (149 mg, 95% yield).¹H NMR (800 MHz, Methanol-d4) δ 8.71 (s, 1H), 7.39 (d, J = 6.4 Hz, 4H), 7.37 – 7.30 (m, 4H), 7.20 (d, J = 7.7 Hz, 1H), 7.13 (dd, J = 16.6, 7.8 Hz, 3H), 6.87 (s, 1H), 6.80 (d, J = 7.8 Hz, 1H), 5.46 (s, 2H), 4.47 – 4.43 (m, 1H), 3.79 – 3.74 (m, 1H), 2.97 (t, J = 7.7 Hz, 2H), 2.46 (t, J = 7.1 Hz, 2H), 2.22 – 2.16 (m, 4H), 2.12 (q, J = 12.5 Hz, 2H), 1.81 (t, J = 8.1 Hz, 2H), 1.67 (q, J = 7.7 Hz, 2H), 1.63 – 1.57 (m, 2H). HRMS (ESI) m/z: calcd for C₃7H40N5O⁺ [M + H]⁺, 570.3227; found, 570.4322. Example 3 Synthesis of Intermediate 3 NS106-166

To a stirred solution of pent-4-yn-1-yl 4-methylbenzenesulfonate (372.5 mg, 2 mmol, 1.0 equiv.) in MeCN (8 mL) were added K2CO3 (552.8 mg, 4 mmol, 2.0 equiv.) and tert-butyl piperazine-1-carboxylate (571.2 mg, 2.4 mmol, 1.2 equiv.). Then the resulting mixture was stirred at 90 ^oC for 12 h. When the reaction was complete, the crude mixture was filtered and purified by silica gel (5% MeOH in CH₂Cl₂) to afford tert- butyl 4-(pent-4-yn-1-yl)piperazine-1-carboxylate as a transparent liquid (444.5 mg, 88% yield). To a solution of previous step product (113.4 mg, 0.45 mmol) and trans-4-(7-(3- Bromobenzyl)-4-imino-5,6-diphenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3- yl)cyclohexanol (166 mg 03 mmol) in triethylamine (05 mL) and DMF (2 mL) were added copper (I) iodide (11.4 mg, 0.06 mmol) and bis(triphenylphosphine)palladium(II) chloride (21.2 mg, 0.03 mmol). The flask was capped and the atmosphere evacuated and backfilled with nitrogen three times. The reaction was heated at 80 ºC for 12 h under nitrogen atmosphere. After cooling to room temperature (RT), the reaction was adsorbed onto Celite and immediately purified by reverse C18 column (eluent: with 10%-100% (v1:v2) methanol in water (contain 0.1% trifluoroacetic acid)) to give the product as a yellow solid. To a mixture of this tert-butyl carbamate, methanol (1 mL) and 4N HCl in dioxane (2 mL) was stirred at 25 ^oC for 1 h. When the reaction was complete, the crude mixture was evaporated under the reduced pressure, the residue was purified by freeze-drying to obtain target NS106-166 (Intermediate 3) (1r,4r)-4- (4-imino-5,6-diphenyl-7-(3-(5-(piperazin-1-yl)pent-1-yn-1-yl)benzyl)-4,7-dihydro- 3H-pyrrolo[2,3-d]pyrimidin-3-yl)cyclohexan-1-ol as a yellow solid (152 mg, 81% yield). ¹H NMR (600 MHz, Methanol-d4) δ 8.75 (s, 1H), 7.40 – 7.36 (m, 6H), 7.33 – 7.26 (m, 4H), 7.18 – 7.14 (m, 2H), 7.07 (s, 1H), 6.92 (d, J = 7.7 Hz, 1H), 5.56 (s, 2H), 4.51 – 4.46 (m, 1H), 4.37 (td, J = 13.2, 3.8 Hz, 2H), 4.11 (t, J = 6.7 Hz, 2H), 3.95 (d, J = 13.7 Hz, 2H), 3.88 – 3.78 (m, 5H), 3.02 (td, J = 7.0, 2.2 Hz, 2H), 2.31 (p, J = 7.0 Hz, 2H), 2.23 (d, J = 10.2 Hz, 2H), 2.20 – 2.14 (m, 4H), 1.68 – 1.59 (m, 2H). HRMS (ESI) m/z: calcd for C40H45N6O⁺ [M + H]⁺, 625.3649; found, 625.7441. General procedure for the synthesis of eEF1A2 degraders.

To a stirred solution of Intermediate 1 or 2 or 3 (0.02 mmol, 1.0 equiv.) in DMF (1 mL) were added amino or acid terminal substituted linkers (0.02 mmol, 1.2 equiv.), HOAt (3.3 mg, 0.024 mmol, 1.2 equiv.), EDCI.HCl (4.6 mg, 0.024 mmol, 1.2 equiv.) and NMM (10.1 mg, 0.1 mmol, 5 equiv.). Then the resulting mixture was stirred at room temperature for 12 h. When the reaction was complete, the crude mixture was purified by preparative HPLC (eluent: with 10%-100% acetonitrile in water which contains 0.1% trifluoroacetic acid), the solution was evaporated under the reduced pressure, the residue was purified by freeze-drying to obtain final eEF1A2 degraders. Example 4 Synthesis of NS106-033

N-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)-7-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-033). To a solution of Intermediate 1 (12.0 mg, 0.02 mmol, 1 equiv) in DMF (1 mL) were added 4-((2- aminoethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (6.3 mg, 0.02 mmol, 1.0 equiv), HOAt (1-hydroxy-7-azabenzo-triazole) (3.3 mg, 0.024 mmol, 1.2 equiv), EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (4.6 mg, 0.024 mmol, 1.2 equiv), and NMM (N-Methylmorpholine) (10.1 mg, 0.1 mmol, 5 equiv). After being stirred overnight at room temperature, the resulting mixture was purified by preparative HPLC (10%-100% acetonitrile / 0.1% TFA in H2O) to afford NS106-033 as a yellow solid (10.4 mg, 58%).¹H NMR (800 MHz, Methanol-d4) δ 8.70 (s, 1H), 7.65 (t, J = 9.5 Hz, 2H), 7.56 (s, 1H), 7.49 (t, J = 8.1 Hz, 1H), 7.38 (d, J = 6.2 Hz, 3H), 7.33 (q, J = 8.5, 6.1 Hz, 3H), 7.16 (dd, J = 15.7, 7.6 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 6.96 (d, J = 7.1 Hz, 1H), 6.88 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 5.45 (s, 2H), 5.01 (dd, J = 12.7, 5.4 Hz, 1H), 4.41 (d, J = 12.5 Hz, 1H), 3.74 (s, 1H), 3.48-3.42 (m, 4H), 2.78 – 2.64 (m, 4H), 2.35 (t, J = 7.0 Hz, 2H), 2.21 – 2.08 (m, 8H), 1.71 (d, J = 8.0 Hz, 2H), 1.61 – 1.51 (m, 4H). HRMS (ESI) m/z: calcd for C53H53N8O6⁺ [M + H]⁺, 897.4083; found, 897.3651. Example 5 Synthesis of NS106-034 N-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propyl)-7-(3- 5 ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-034). NS106-034 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 1 and 4-((3-aminopropyl)amino)-2-(2,6-dioxopiperidin-3- yl)isoindoline-1,3-dione. (yellow solid, 9.0 mg, 49%) ¹H NMR (800 MHz, Methanol- 10 d₄) δ 8.70 (s, 1H), 7.64 (d, J = 10.9 Hz, 1H), 7.56 (s, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 7.2 Hz, 3H), 7.33 (d, J = 7.6 Hz, 3H), 7.16 (dd, J = 26.5, 7.7 Hz, 3H), 7.09 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 8.5 Hz, 1H), 6.95 (d, J = 7.0 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.43 (s, 2H), 5.06 – 5.01 (m, 1H), 4.41 (d, J = 12.9 Hz, 1H), 3.75 (s, 1H), 3.41 – 3.32 (m, 4H), 2.84-2.77 (m, 2H), 2.70 (t, J = 14.3 Hz, 2H), 2.39 (t, J = 7.0 15 Hz, 2H), 2.25 – 2.06 (m, 8H), 1.84 (t, J = 6.9 Hz, 2H), 1.76 (t, J = 7.9 Hz, 2H), 1.59 (d, J = 9.9 Hz, 4H). HRMS (ESI) m/z: calcd for C₅₄H₅₅N₈O₆ ⁺ [M + H]⁺, 911.4239; found, 911.4142. Example 6 20 Synthesis of NS106-035

N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-7-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-035). NS106-035 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((4-aminobutyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline- 1,3-dione. (yellow solid, 9.8 mg, 53%) ¹H NMR (800 MHz, Methanol-d4) δ 8.67 (s, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 7.2 Hz, 4H), 7.31 (t, J = 7.7 Hz, 4H), 7.21– 7.06 (m, 4H), 6.96 (t, J = 6.8 Hz, 2H), 6.84 (s, 1H), 6.76 (d, J = 7.9 Hz, 1H), 5.41 (s, 2H), 5.02 (dd, J = 12.0, 3.6 Hz, 1H), 4.41 (d, J = 12.1 Hz, 1H), 3.77 (d, J = 12.9 Hz, 1H), 3.25 (t, J = 7.1 Hz, 2H), 3.21 (t, J = 6.9 Hz, 2H), 2.87– 2.77 (m, 1H), 2.70 (t, J = 13.4 Hz, 2H), 2.36 (t, J = 7.0 Hz, 2H), 2.20-2.12 (m, 9H), 1.78-1.72 (m, 2H), 1.65 (t, J = 7.6 Hz, 2H), 1.62– 1.54 (m, 4H), 1.48-1.43 (m, 2H). HRMS (ESI) m/z: calcd for C55H57N8O6⁺ [M + H]⁺, 925.4396; found, 925.8635. Example 7 Synthesis of NS106-036 N-(5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)pentyl)-7-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-036). NS106-036 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 1 and 4-((5-aminopentyl)amino)-2-(2,6-dioxopiperidin-3- yl)isoindoline-1,3-dione. (yellow solid, 8.5 mg, 45%)¹H NMR (800 MHz, Methanol- d₄) δ 8.69 (s, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 7.1 Hz, 4H), 7.32 (t, J = 7.7 Hz, 4H), 7.20 – 7.07 (m, 4H), 6.98 (t, J = 6.8 Hz, 2H), 6.85 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 5.42 (s, 2H), 5.03 (dd, J = 12.0, 3.6 Hz, 1H), 4.41 (d, J = 12.1 Hz, 1H), 3.76 (d, J 101 = 13.7 Hz, 1H), 3.28 (t, J = 7.1 Hz, 2H), 3.20 (t, J = 6.9 Hz, 2H), 2.85 – 2.78 (m, 1H), 2.70 (t, J = 13.4 Hz, 2H), 2.38 (t, J = 7.0 Hz, 2H), 2.18-2.11 (m, 9H), 1.74 (q, J = 7.6 Hz, 2H), 1.66 (t, J = 7.6 Hz, 2H), 1.63 – 1.53 (m, 6H), 1.45 (q, J = 7.9 Hz, 2H). HRMS (ESI) m/z: calcd for C₅₆H₅₉N₈O₆ ⁺ [M + H]⁺, 939.4552; found, 939.4130. Example 8 Synthesis of NS106-037

N-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)-7-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-037). NS106-037 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((6-aminohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline- 1,3-dione. (yellow solid, 9.0 mg, 47%)¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 6.3 Hz, 4H), 7.32 (d, J = 7.7 Hz, 4H), 7.16-7.12 (m, 4H), 7.00 (d, J = 6.9 Hz, 1H), 6.97 (d, J = 8.6 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 5.43 (s, 2H), 5.03 (dd, J = 12.9, 5.3 Hz, 1H), 4.41 (d, J = 12.4 Hz, 1H), 3.75 (s, 1H), 3.26 (t, J = 7.3 Hz, 2H), 3.21 – 3.16 (m, 2H), 2.87 – 2.80 (m, 1H), 2.75 – 2.65 (m, 2H), 2.38 (t, J = 7.0 Hz, 2H), 2.24 – 2.00 (m, 9H), 1.75 (t, J = 7.8 Hz, 2H), 1.61-1.55 (m, 8H), 1.46 – 1.34 (m, 4H). HRMS (ESI) m/z: calcd for C₅₇H₆₁N₈O₆ ⁺ [M + H]⁺, 953.4709; found, 953.4126. Example 9 Synthesis of NS106-038 N-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)heptyl)-7-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-038). NS106-038 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 1 and 4-((7-aminoheptyl)amino)-2-(2,6-dioxopiperidin-3- yl)isoindoline-1,3-dione. (yellow solid, 8.8 mg, 45%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.50 (t, J = 8.1 Hz, 1H), 7.38 (d, J = 6.9 Hz, 4H), 7.32 (d, J = 7.2 Hz, 4H), 7.20 – 7.07 (m, 4H), 6.99-6.95 (m, 2H), 6.85 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.43 (s, 2H), 5.03 (dd, J = 13.3, 5.7 Hz, 1H), 4.42 (d, J = 13.8 Hz, 1H), 3.76 (d, J = 12.2 Hz, 1H), 3.24 (t, J = 7.1 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 2.85 – 2.79 (m, 1H), 2.71 (t, J = 16.7 Hz, 2H), 2.38 (t, J = 7.1 Hz, 2H), 2.23 – 1.97 (m, 9H), 1.74 (d, J = 8.0 Hz, 2H), 1.66 – 1.44 (m, 8H), 1.41-1.33 (m, 6H). HRMS (ESI) m/z: calcd for C₅₈H₆₃N₈O₆ ⁺ [M + H]⁺, 967.4865; found, 967.4125. Example 10 Synthesis of NS106-039 N-(8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)-7-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (NS106-039). NS106-039 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((8-aminooctyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline- 1,3-dione. (yellow solid, 9.8 mg, 50%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.38 (d, J = 6.0 Hz, 4H), 7.35 – 7.26 (m, 4H), 7.19 – 7.07 (m, 4H), 7.00 (dd, J = 11.0, 7.9 Hz, 2H), 6.84 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.44 (s, 2H), 5.06 – 5.01 (m, 1H), 4.41 (d, J = 13.4 Hz, 1H), 3.74 (d, J = 11.6 Hz, 1H), 3.26 (s, 2H), 3.16 (s, 2H), 2.86 – 2.81 (m, 1H), 2.75-2.67 (m, 2H), 2.38 (t, J = 7.2 Hz, 2H), 2.22 – 2.07 (m, 9H), 1.77 – 1.71 (m, 2H), 1.63 – 1.55 (m, 6H), 1.49 (t, J = 6.8 Hz, 2H), 1.38- 1.33 (m, 8H).HRMS (ESI) m/z: calcd for C59H65N8O6⁺ [M + H]⁺, 981.5022; found, 981.3625. Example 11 Synthesis of NS106-084

N-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamide. NS106-084 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((2-(2-aminoethoxy)ethyl)amino)-2-(2,6- dioxopiperidin-3-yl)isoindoline-1,3-dione. (yellow solid, 8.9 mg, 47%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.70 (s, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.39 (t, J = 6.4 Hz, 5H), 7.34 – 7.32 (m, 3H), 7.14 (d, J = 7.7 Hz, 3H), 7.11 (d, J = 7.7 Hz, 1H), 7.08 (d, J = 7.9 Hz, 1H), 7.01 (d, J = 7.1 Hz, 1H), 6.87 (s, 1H), 6.77 (d, J = 7.9 Hz, 1H), 5.43 (s, 2H), 5.02 (dd, J = 11.9, 6.0 Hz, 1H), 4.43 (d, J = 11.9 Hz, 1H), 3.76 (s, 2H), 3.68 (s, 1H), 3.57 (d, J = 5.4 Hz, 2H), 3.47 (d, J = 5.3 Hz, 2H), 3.39 (t, J = 5.3 Hz, 2H), 3.06 (s, 1H), 2.93 (s, 1H), 2.69-2.63 (m, 2H), 2.42 – 2.40 (m, 2H), 2.22-2.15 (m, 8H), 1.74 (d, J = 7.4 Hz, 2H), 1.62 – 1.59 (m, 4H). HRMS (ESI) m/z: calcd for C55H57N8O7⁺ [M + H]⁺, 941.4345; found, 941.7128. Example 12 Synthesis of NS106-085

N-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethoxy)ethyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamide. NS106-085 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((2-(2-(2- aminoethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione. (yellow solid, 9.1 mg, 46%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.67 – 7.62 (m, 1H), 7.56 (s, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.4 Hz, 3H), 7.35 – 7.32 (m, 3H), 7.19-7.11 (m, 3H), 7.04 (d, J = 8.5 Hz, 1H), 7.02 (d, J = 7.0 Hz, 1H), 6.87 (s, 1H), 6.78 (d, J = 8.2 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 12.5, 5.5 Hz, 1H), 4.42 (d, J = 6.2 Hz, 1H), 3.77 – 3.73 (m, 1H), 3.70 (t, J = 5.3 Hz, 2H), 3.66 – 3.60 (m, 4H), 3.54 (t, J = 5.5 Hz, 2H), 3.46 (t, J = 5.3 Hz, 2H), 3.35 (s, 2H), 3.06 (s, 1H), 2.93 (s, 1H), 2.73 – 2.66 (m, 2H), 2.36 (t, J = 7.0 Hz, 2H), 2.19 – 2.06 (m, 8H), 1.75 – 1.70 (m, 2H), 1.59- 1.53 (m, 4H). HRMS (ESI) m/z: calcd for C57H61N8O8⁺ [M + H]⁺, 985.4607; found, 985.4802. Example 13 Synthesis of NS106-086 N-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethoxy)ethoxy)ethyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamide. NS106-086 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3- dione. (yellow solid, 8.4 mg, 41%) ¹H NMR (800 MHz, Methanol-d4) δ 8.70 (s, 1H), 7.66 – 7.63 (m, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.9 Hz, 3H), 7.33 (d, J = 7.7 Hz, 3H), 7.19-7.13 (m, 3H), 7.10 (d, J = 7.9 Hz, 1H), 7.05 (d, J = 8.5 Hz, 1H), 7.02 (d, J = 6.8 Hz, 1H), 6.87 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 13.5, 5.5 Hz, 1H), 4.42 (d, J = 11.4 Hz, 1H), 3.74 (d, J = 10.9 Hz, 1H), 3.70 (t, J = 5.3 Hz, 2H), 3.66-3.61 (m, 6H), 3.58 (d, J = 4.7 Hz, 2H), 3.51 (t, J = 5.3 Hz, 2H), 3.47 (t, J = 5.2 Hz, 2H), 3.33 (s, 2H), 2.81 – 2.70 (m, 4H), 2.37 (t, J = 7.0 Hz, 2H), 2.20 – 2.09 (m, 8H), 1.75 – 1.71 (m, 2H), 1.59-1.51 (m, 4H). HRMS (ESI) m/z: calcd for C₅₉H₆₅N₈O₉ ⁺ [M + H]⁺, 1029.4869; found, 1029.6606. Example 14 Synthesis of NS106-087 N-(14-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12- tetraoxatetradecyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide. NS106-087 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 1 and 4-((14-amino-3,6,9,12-tetraoxatetradecyl)amino)-2-(2,6- dioxopiperidin-3-yl)isoindoline-1,3-dione. (yellow solid, 8.8 mg, 41%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.70 (s, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.39 (s, 3H), 7.33 (s, 3H), 7.19 – 7.15 (m, 3H), 7.11 (d, J = 7.9 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 12.6, 5.6 Hz, 1H), 4.43 (d, J = 12.6 Hz, 1H), 3.76 (s, 1H), 3.70 (t, J = 5.2 Hz, 2H), 3.67 – 3.59 (m, 10H), 3.56 (d, J = 5.0 Hz, 2H), 3.51 (t, J = 5.4 Hz, 2H), 3.47 (t, J = 5.2 Hz, 2H), 3.34 (t, J = 5.9 Hz, 2H), 2.82 – 2.67 (m, 4H), 2.38 (t, J = 6.9 Hz, 2H), 2.19-2.11 (m, 8H), 1.76 – 1.72 (m, 2H), 1.62 – 1.57 (m, 4H). HRMS (ESI) m/z: calcd for C61H69N8O10⁺ [M + H]⁺, 1073.5131; found, 1073.4140. Example 15 Synthesis of NS106-088 N-(17-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12,15- pentaoxaheptadecyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamide. NS106-088 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-((17-amino-3,6,9,12,15- pentaoxaheptadecyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione. (yellow solid, 9.4 mg, 42%) ¹H NMR (800 MHz, Methanol-d4) $ 8.70 (s, 1H), 7.67 – 7.63 (m, 1H), 7.56 (s, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.4 Hz, 3H), 7.34 (s, 3H), 7.19- 7.12 (m, 3H), 7.11 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 7.03 (d, J = 7.1 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 8.3 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 12.7, 5.5 Hz, 1H), 4.43 (d, J = 12.0 Hz, 1H), 3.76 (d, J = 7.2 Hz, 1H), 3.70 (t, J = 5.3 Hz, 2H), 3.65 – 3.57 (m, 16H), 3.52 (t, J = 5.4 Hz, 2H), 3.47 (t, J = 5.3 Hz, 2H), 3.34 (t, J = 5.4 Hz, 2H), 2.83 – 2.69 (m, 4H), 2.39 (d, J = 6.7 Hz, 2H), 2.19 – 2.11 (m, 8H), 1.74 (d, J = 7.9 Hz, 2H), 1.65-1.55 (m, 4H). HRMS (ESI) m/z: calcd for C63H73N8O11⁺ [M + H]⁺, 1117.5393; found, 1117.5914. Example 16 Synthesis of NS113-167

N-(6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)-7-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamide (113167). NS113-167 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 3-(4-(6-aminohex-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6- dione. (yellow solid, 6.2 mg, 34%) ¹H NMR (600 MHz, Methanol-d₄) δ8.69 (s, 1H), 7.69 (dd, J = 7.6, 1.0 Hz, 1H), 7.56 (dd, J = 7.7, 1.0 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.41 – 7.36 (m, 4H), 7.35 – 7.29 (m, 4H), 7.18 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.09 (t, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.77 (d, J = 7.7 Hz, 1H), 5.43 (s, 2H), 5.14 (dd, J = 13.3, 5.2 Hz, 1H), 4.49 (d, J = 17.4 Hz, 1H), 4.46-4.41 (m, 2H), 3.78 – 3.73 (m, 1H), 3.25 (dt, J = 7.5, 3.8 Hz, 2H), 2.92 – 2.84 (m, 2H), 2.78-2.74 (m, 1H), 2.50 (t, J = 6.6 Hz, 3H), 2.37 (t, J = 7.0 Hz, 2H), 2.22 (t, J = 7.4 Hz, 2H), 2.18 – 2.06 (m, 6H), 1.77 – 1.65 (m, 6H), 1.61 – 1.55 (m, 4H). HRMS (ESI) m/z: calcd for C₅₇H₅₈N₇O₅ ⁺ [M + H]⁺, 920.4494; found, 920.5739. Example 17 Synthesis of NS106-094

(2S,4R)-4-hydroxy-1-((S)-2-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS106-094 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)-2-amino-3,3- dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide. (yellow solid, 8.8 mg, 44%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.87 (s, 1H), 8.71 (s, 1H), 8.63 (t, J = 6.1 Hz, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.42 – 7.37 (m, 5H), 7.35 – 7.31 (m, 3H), 7.19 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.64 (d, J = 9.0 Hz, 1H), 4.56 (t, J = 7.9 Hz, 1H), 4.53 (d, J = 6.3 Hz, 1H), 4.50 (s, 1H), 4.44 (d, J = 12.9 Hz, 2H), 4.38 – 4.34 (m, 1H), 3.90 (d, J = 11.0 Hz, 1H), 3.81 (dd, J = 11.0, 3.9 Hz, 1H), 3.76 (s, 1H), 2.46 (s, 3H), 2.40 (d, J = 6.9 Hz, 2H), 2.36-2.31 (m, 3H), 2.21 – 2.10 (m, 7H), 1.79 – 1.73 (m, 2H), 1.60 (d, J = 9.0 Hz, 3H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₀H₆₇N₈O₅S ⁺ [M + H]⁺, 1011.4950; found, 1011.4533. Example 18 Synthesis of NS106-040

(2S,4R)-4-hydroxy-1-((S)-2-(2-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)acetamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-040 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(2-aminoacetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.0 mg, 42%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.87 (s, 1H), 8.71 (s, 1H), 7.45 (t, J = 11.2 Hz, 2H), 7.42 – 7.36 (m, 4H), 7.36 – 7.23 (m, 4H), 7.16-7.11 (m, 6H), 6.86 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.52 (m, 2H), 4.49 (s, 1H), 4.46 – 4.40 (m, 1H), 4.33 (d, J = 15.4 Hz, 1H), 3.90-3.85 (m, 3H), 3.81 – 3.72 (m, 2H), 2.46 (s, 3H), 2.39 (d, J = 7.2 Hz, 2H), 2.32 (t, J = 7.5 Hz, 2H), 2.24 – 2.05 (m, 8H), 1.78 (t, J = 7.8 Hz, 2H), 1.64 – 1.52 (m, 4H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C62H70N9O6S⁺ [M + H]⁺, 1068.5164; found, 1068.4193. Example 19 Synthesis of NS106-041

(2S,4R)-4-hydroxy-1-((S)-2-(3-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)propanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-041 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(3-aminopropanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.7 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.86 (s, 1H), 8.72 (s, 1H), 8.62 (t, J = 6.1 Hz, 1H), 7.95 (s, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.48 – 7.42 (m, 2H), 7.41 – 7.37 (m, 4H), 7.35 – 7.30 (m, 3H), 7.20 – 7.08 (m, 4H), 6.86 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.60 (d, J = 8.7 Hz, 1H), 4.58 – 4.52 (m, 2H), 4.49 (s, 1H), 4.43 (s, 1H), 4.38-4.31 (m, 1H), 3.91 (d, J = 10.9 Hz, 1H), 3.81 – 3.73 (m, 2H), 3.46 (q, J = 6.7 Hz, 1H), 3.39 (dt, J = 13.3, 6.3 Hz, 1H), 2.56 – 2.42 (m, 5H), 2.38 (t, J = 7.0 Hz, 2H), 2.28 – 2.03 (m, 10H), 1.72 (q, J = 7.8 Hz, 2H), 1.63 – 1.50 (m, 4H), 1.02 (s, 9H).HRMS (ESI) m/z: calcd for C₆₃H₇₂N₉O₆S⁺ [M + H]⁺, 1082.5321; found, 1082.4216. Example 20 Synthesis of NS106-042

(2S,4R)-4-hydroxy-1-((S)-2-(4-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)butanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-042 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(4-aminobutanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.3 mg, 42%) ¹H NMR (800 MHz, Methanol-d4) δ 8.88 (s, 1H), 8.72 (s, 1H), 7.51 – 7.42 (m, 2H), 7.40 (d, J = 22.8 Hz, 4H), 7.33 (q, J = 7.6 Hz, 4H), 7.21 – 6.91 (m, 6H), 6.86 (s, 1H), 6.78 (d, J = 8.0 Hz, 1H), 5.45 (s, 2H), 4.61 (s, 1H), 4.59 – 4.52 (m, 2H), 4.49 (s, 1H), 4.42 (d, J = 13.1 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 11.0 Hz, 1H), 3.83 – 3.71 (m, 2H), 3.19 (d, J = 6.1 Hz, 2H), 2.46 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.33-2.28 (m, 2H), 2.23 – 2.09 (m, 10H), 1.78-1.73 (m, 4H), 1.59-1.55 (m, 4H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C64H74N9O6S⁺ [M + H]⁺, 1096.5477; found, 1096.6245. Example 21 Synthesis of NS106-043

(2S,4R)-4-hydroxy-1-((S)-2-(5-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)pentanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-043 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(5-aminopentanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.4 mg, 42%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.88 (s, 1H), 8.72 (s, 1H), 7.49 – 7.26 (m, 11H), 7.16-7.11 (m, 5H), 6.86 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 5.45 (s, 2H), 4.62 (s, 1H), 4.58 – 4.52 (m, 2H), 4.49 (s, 1H), 4.42 (d, J = 13.0 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 11.0 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.21 – 3.13 (m, 2H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.32 – 2.25 (m, 2H), 2.22 – 2.09 (m, 10H), 1.74 (t, J = 7.8 Hz, 2H), 1.65 – 1.48 (m, 8H), 1.02 (s, 9H). HRMS (ESI) m/z: calcd for C₆₅H₇₆N₉O₆S⁺ [M + H]⁺, 1110.5634; found, 1110.3777. Example 22 Synthesis of NS106-044

(2S,4R)-4-hydroxy-1-((S)-2-(6-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)hexanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-044 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(6-aminohexanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 10.2 mg, 45%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.46 (d, J = 7.9 Hz, 2H), 7.43 – 7.36 (m, 5H), 7.33 (q, J = 7.5 Hz, 4H), 7.18-7.11 (m, 5H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.60 – 4.48 (m, 3H), 4.43 (d, J = 12.4 Hz, 1H), 4.35 (d, J = 15.3 Hz, 1H), 3.90 (d, J = 11.0 Hz, 1H), 3.83 – 3.74 (m, 2H), 3.16 (d, J = 7.5 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 7.1 Hz, 2H), 2.32 – 2.25 (m, 2H), 2.23 – 2.11 (m, 8H), 1.74 (t, J = 7.7 Hz, 2H), 1.61-1.55 (m, 6H), 1.50 (t, J = 7.6 Hz, 2H), 1.35 (d, J = 9.2 Hz, 2H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₆₆H₇₈N₉O₆S⁺ [M + H]⁺, 1124.5790; found, 1124.4813. Example 23 Synthesis of NS106-045

(2S,4R)-4-hydroxy-1-((S)-2-(7-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)heptanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-045 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(7-aminoheptanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.2 mg, 40%) ¹H NMR (800 MHz, Methanol-d4) δ 8.87 (s, 1H), 8.72 (s, 1H), 7.53 – 7.24 (m, 10H), 7.21 – 6.94 (m, 6H), 6.86 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.57 (t, J = 8.5 Hz, 1H), 4.53 (d, J = 15.4 Hz, 1H), 4.49 (s, 1H), 4.43 (s, 1H), 4.35 (d, J = 15.2 Hz, 1H), 3.90 (d, J = 11.3 Hz, 1H), 3.82 – 3.74 (m, 2H), 3.15 (s, 2H), 2.47 (s, 3H), 2.38 (t, J = 7.0 Hz, 2H), 2.31 – 1.98 (m, 12H), 1.77 – 1.69 (m, 2H), 1.68 – 1.52 (m, 6H), 1.49 (s, 2H), 1.33 (s, 4H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C67H80N9O6S⁺ [M + H]⁺, 1138.5947; found, 1138.2855. Example 24 Synthesis of NS106-046

(2S,4R)-4-hydroxy-1-((S)-2-(8-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)octanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-046 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(8-aminooctanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.4 mg, 41%) ¹H NMR (800 MHz, Methanol-d4) δ 8.87 (s, 1H), 8.72 (s, 1H), 7.54 – 7.25 (m, 10H), 7.22 – 6.96 (m, 6H), 6.85 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.51 (m, 2H), 4.49 (s, 1H), 4.43 (s, 1H), 4.35 (d, J = 15.6 Hz, 1H), 3.89 (d, J = 11.0 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.15 (d, J = 7.3 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.31 – 1.98 (m, 12H), 1.74 (t, J = 7.9 Hz, 2H), 1.59-1.54 (m, 6H), 1.48 (s, 2H), 1.34-1.29 (m, 6H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C68H82N9O6S⁺ [M + H]⁺, 1152.6103; found, 1152.6403. Example 25 Synthesis of NS106-047

(2S,4R)-4-hydroxy-1-((S)-2-(9-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)nonanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-047 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(9-aminononanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 9.6 mg, 41%) ¹H NMR (800 MHz, Methanol-d4) δ 8.88 (s, 1H), 8.72 (s, 1H), 7.48 – 7.29 (m, 12H), 7.17-7.11 (m, 4H), 6.85 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.45 (s, 3H), 4.64 (s, 1H), 4.57 – 4.51 (m, 2H), 4.49 (s, 1H), 4.42 (d, J = 11.5 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 10.9 Hz, 1H), 3.82 – 3.75 (m, 2H), 3.15 (d, J = 7.4 Hz, 2H), 2.47 (s, 3H), 2.38 (d, J = 7.1 Hz, 2H), 2.27 – 2.11 (m, 12H), 1.74 (t, J = 7.8 Hz, 2H), 1.60 – 1.54 (m, 6H), 1.48 (t, J = 6.9 Hz, 2H), 1.31 (s, 8H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C69H84N9O6S⁺ [M + H]⁺, 1166.6260; found, 1166.7456. Example 26 Synthesis of NS106-048

(2S,4R)-4-hydroxy-1-((S)-2-(10-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)decanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-048 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(10-aminodecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 10.1 mg, 43%) ¹H NMR (800 MHz, Methanol-d4) δ 8.88 (s, 1H), 8.72 (s, 1H), 7.50 – 7.27 (m, 11H), 7.23 – 7.04 (m, 5H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.52 (m, 2H), 4.49 (s, 1H), 4.44 (d, J = 12.5 Hz, 1H), 4.35 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 11.0 Hz, 1H), 3.82 – 3.74 (m, 2H), 3.15 (d, J = 7.2 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.30 – 2.09 (m, 12H), 1.77 – 1.71 (m, 2H), 1.63 – 1.55 (m, 6H), 1.52 – 1.46 (m, 2H), 1.30 (s, 10H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₇₀H₈₆N₉O₆S⁺ [M + H]⁺, 1180.6416; found, 1180.6019. Example 27 Synthesis of NS106-049 (2S,4R)-4-hydroxy-1-((S)-2-(11-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept- 6-ynamido)undecanamido)-3,3-dimethylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-049 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-1-((S)- 2-(11-aminoundecanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol- 5-yl)benzyl)pyrrolidine-2-carboxamide. (white solid, 8.8 mg, 37%) ¹H NMR (800 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.52 – 7.27 (m, 11H), 7.20 – 6.99 (m, 5H), 6.85 (s, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.52 (m, 2H), 4.49 (s, 1H), 4.43 (s, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 11.1 Hz, 1H), 3.82 – 3.75 (m, 2H), 3.15 (s, 2H), 2.47 (s, 3H), 2.39 (t, J = 7.2 Hz, 2H), 2.30 – 2.08 (m, 12H), 1.74 (t, J = 7.8 Hz, 2H), 1.61-1.56 (m, 6H), 1.50 – 1.45 (m, 2H), 1.31-1.26 (m, 12H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C71H88N9O6S⁺ [M + H]⁺, 1194.6573; found, 1194.6581. Example 28 10 Synthesis of NS113-044

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((2-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6-15 ynamido)ethyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-044 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((2-aminoethyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 10.1 mg, 42%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.47 – 7.42 (m, 4H), 7.40 – 7.36 (m, 4H), 7.35 – 7.30 (m, 4H), 7.20 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.9 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.34 (d, J = 6.9 Hz, 1H), 4.76 – 4.72 (m, 1H), 461 – 457 (m 1H) 444 (s 2H) 383 (d J = 112 Hz 1H) 376 (dd J = 113 35 Hz 2H), 3.28 – 3.23 (m, 1H), 3.23 – 3.16 (m, 3H), 2.82 (dd, J = 14.3, 6.8 Hz, 1H), 2.74 (dd, J = 14.3, 7.5 Hz, 1H), 2.46 (s, 3H), 2.37 (t, J = 7.0 Hz, 2H), 2.18-2.12 (m, 9H), 1.98- 1.93 (m, 1H), 1.74-1.70 (m, 2H), 1.61 – 1.52 (m, 4H), 1.35 – 1.28 (m, 4H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C₆₈H₇₈FN₁₀O₇S⁺ [M + H]⁺, 1197.5754; found, 1197.5733. Example 29 Synthesis of NS113-045

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((3-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)propyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-045 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((3-aminopropyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 11.3 mg, 47%) ¹H NMR (600 MHz, Methanol-d4) δ 8.91 (s, 1H), 8.72 (s, 1H), 7.45 (q, J = 8.4 Hz, 4H), 7.41 – 7.37 (m, 4H), 7.34 – 7.30 (m, 4H), 7.19 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.9 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.33 (dd, J = 8.3, 6.0 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.61 – 4.57 (m, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.2 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.17 (dt, J = 13.6, 6.7 Hz, 1H), 3.09 – 3.05 (m, 1H), 3.03 – 2.96 (m, 2H), 2.87 – 2.83 (m, 1H), 2.74 (dd, J = 14.1, 8.4 Hz, 1H), 2.46 (s, 3H), 2.37 (d, J = 6.9 Hz, 2H), 2.21 – 2.07 (m, 9H), 1.95 (td, J = 9.2, 4.7 Hz, 1H), 1.72 (dd, J = 9.1, 6.3 Hz, 2H), δ.62 – 1.51 (m, 6H), 1.34 – 1.27 (m, 4H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C69H80FN10O7S⁺ [M + H]⁺, 1211.5911; found, 1211.5847. Example 30 Synthesis of NS113-046

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((4-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)butyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-046 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((4-aminobutyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 10.8 mg, 44%) ¹H NMR (600 MHz, Methanol-d4) $ 8.87 (s, 1H), 8.72 (s, 1H), 7.44 (d, J = 1.7 Hz, 4H), 7.39 (dd, J = 5.3, 2.0 Hz, 4H), 7.35 – 7.29 (m, 4H), 7.18 (d, J = 7.7 Hz, 1H), 7.16 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (d, J = 8.1 Hz, 1H), 4.73 (d, J = 9.3 Hz, 1H), 4.57 (t, J = 8.5 Hz, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.2 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.15 – 3.05 (m, 4H), 2.86 – 2.82 (m, 1H), 2.76 – 2.72 (m, 1H), 2.47 (s, 3H), 2.38 (t, J = 7.0 Hz, 2H), 2.23 – 2.08 (m, 9H), 1.97 – 1.94 (m, 1H), 1.74 – 1.69 (m, 2H), 1.62 – 1.53 (m, 4H), 1.39 – 1.30 (m, 8H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₇S⁺ [M + H]⁺, 1225.6067; found, 1225.5886. Example 31 Synthesis of NS113-047

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((5-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)pentyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-047 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((5-aminopentyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 12.4 mg, 50%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.48 – 7.42 (m, 4H), 7.40-7.37 (m, 4H), 7.34 – 7.30 (m, 4H), 7.19 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.3, 6.0 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.59 – 4.56 (m, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 3.9 Hz, 2H), 3.12 – 3.03 (m, 4H), 2.83 (dd, J = 14.1, 6.0 Hz, 1H), 2.73 (dd, J = 14.1, 8.4 Hz, 1H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.22 – 2.08 (m, 9H), 1.98-1.94 (m, 1H), 1.76 – 1.70 (m, 2H), 1.59-1.56 (m, 4H), 1.42 – 1.30 (m, 8H), 1.19 (t, J = 7.8 Hz, 2H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C71H84FN10O7S⁺ [M + H]⁺, 1239.6224; found, 1239.6065. Example 32 Synthesis of NS113-048

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((6-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)hexyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-048 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((6-aminohexyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 10.0 mg, 40%) ¹H NMR (600 MHz, Methanol-d4) δ 8.93 (s, 1H), 8.72 (s, 1H), 7.48 – 7.42 (m, 4H), 7.39-7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (dd, J = 7.8, 1.5 Hz, 1H), 7.15-7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (t, J = 1.9 Hz, 1H), 6.80 – 6.77 (m, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.4, 5.9 Hz, 1H), 4.74 (d, J = 9.3 Hz, 1H), 4.60 – 4.56 (m, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.11 – 3.01 (m, 4H), 2.85 – 2.82 (m, 1H), 2.73 (dd, J = 14.1, 8.5 Hz, 1H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.21 – 2.09 (m, 9H), 1.97 – 1.93 (m, 1H), 1.76 – 1.72 (m, 2H), 1.59-1.55 (m, 4H), 1.41 (d, J = 7.5 Hz, 2H), 1.36 – 1.25 (m, 8H), 1.16 (t, J = 7.8 Hz, 2H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C72H86FN10O7S⁺ [M + H]⁺, 1253.6380; found, 1253.6380. Example 33 Synthesis of NS113-049

hydroxy-N-((S)-3-((7-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)heptyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-049 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((7-aminoheptyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 10.4 mg, 41%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.47 – 7.43 (m, 4H), 7.39-7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (d, J = 7.6 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.4, 5.9 Hz, 1H), 4.74 (d, J = 9.1 Hz, 1H), 4.59 – 4.56 (m, 1H), 4.44 (d, J = 4.4 Hz, 2H), 3.83 (d, J = 11.2 Hz, 1H), 3.76 (dd, J = 11.0, 3.9 Hz, 2H), 3.09 (q, J = 6.9 Hz, 3H), 3.03 – 3.00 (m, 1H), 2.83 (dd, J = 14.0, 5.9 Hz, 1H), 2.75 – 2.71 (m, 1H), 2.47 (s, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.22 – 2.12 (m, 9H), 1.98 – 1.94 (m, 1H), 1.76 – 1.72 (m, 2H), 1.59 (dd, J = 14.7, 7.8 Hz, 4H), 1.42 (t, J = 7.1 Hz, 2H), 1.35 – 1.27 (m, 8H), 1.25 – 1.21 (m, 4H), 1.06 (s, 9H).HRMS (ESI) m/z: calcd for C₇₃H₈₈FN₁₀O₇S⁺ [M + H]⁺, 1267.6537; found, 1267.6548. Example 34 Synthesis of NS113-050

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((8-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)octyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-050 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((8-aminooctyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 11.5 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.46 – 7.42 (m, 4H), 7.40 – 7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.20 – 7.17 (m, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.5, 5.8 Hz, 1H), 4.74 (d, J = 9.2 Hz, 1H), 4.60 – 4.56 (m, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 3.9 Hz, 2H), 3.13-3.08 (m, 3H), 3.02 – 2.99 (m, 1H), 2.86 – 2.82 (m, 1H), 2.75 – 2.71 (m, 1H), 2.47 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.12 (m, 9H), 1.98 – 1.95 (m, 1H), 1.75 (q, J = 7.6 Hz, 2H), 1.62 – 1.56 (m, 4H), 1.43 – 1.39 (m, 2H), 1.35 – 1.29 (m, 6H), 1.20 (d, J = 6.0 Hz, 6H), 1.11 (s, 2H), 1.06 (s, 9H).HRMS (ESI) m/z: calcd for C₇₄H₉₀FN₁₀O₇S+ [M + H]⁺, 1281.6693; found, 1281.6537. Example 35 Synthesis of NS113-051

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((9-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)nonyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-051 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((9-aminononyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 12.7 mg, 49%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.91 (s, 1H), 8.73 (s, 1H), 7.48 – 7.42 (m, 4H), 7.42 – 7.37 (m, 4H), 7.36 – 7.31 (m, 4H), 7.22 – 7.18 (m, 1H), 7.16 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.46 (s, 2H), 5.32 (dd, J = 8.5, 5.8 Hz, 1H), 4.75 (d, J = 9.2 Hz, 1H), 4.61 – 4.56 (m, 1H), 4.45 (s, 2H), 3.84 (d, J = 11.1 Hz, 1H), 3.79-3.74 (m, 2H), 3.14-3.08 (m, 3H), 3.03 – 2.99 (m, 1H), 2.87 – 2.83 (m, 1H), 2.76– 2.71 (m, 1H), 2.49 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.24 – 2.12 (m, 9H), 1.99 – 1.96 (m, 1H), 1.78-1.74 (m, 2H), 1.63 – 1.56 (m, 6H), 1.44 – 1.39 (m, 2H), 1.36 – 1.29 (m, 6H), 1.20 (d, J = 6.0 Hz, 6H), 1.12 (s, 2H), 1.07 (s, 9H). HRMS (ESI) m/z: calcd for C₇₅H₉₂FN₁₀O₇S⁺ [M + H]⁺, 1295.6850; found, 1295.6678. Example 36 Synthesis of NS113-052

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((10-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)decyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-052 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((10-aminodecyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 10.9 mg, 42%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.93 (s, 1H), 8.72 (s, 1H), 7.46 – 7.43 (m, 4H), 7.39-7.36 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (dt, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (t, J = 1.8 Hz, 1H), 6.80 – 6.78 (m, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.5, 5.8 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.60 – 4.56 (m, 1H), 4.46 – 4.42 (m, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 3.9 Hz, 2H), 3.14 (t, J = 7.1 Hz, 2H), 3.12 – 3.08 (m, 1H), 3.01 (d, J = 6.7 Hz, 1H), 2.86 – 2.82 (m, 1H), 2.75 – 2.71 (m, 1H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.11 (m, 9H), 1.97 – 1.94 (m, 1H), 1.75 (dd, J = 8.6, 6.7 Hz, 2H), 1.61 – 1.56 (m, 4H), 1.46 – 1.43 (m, 2H), 1.36 – 1.30 (m, 6H), 1.20 (d, J = 27.6 Hz, 8H), 1.10 (s, 2H), 1.06 (s, 9H).HRMS (ESI) m/z: calcd for C₇₆H₉₄FN₁₀O₇S⁺ [M + H]⁺, 1309.7006; found, 1309.8124. Example 37 Synthesis of NS113-053

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((11-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)undecyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-053 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((11-aminoundecyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2- (1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine- 2-carboxamide. (white solid, 9.8 mg, 37%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.47 – 7.42 (m, 4H), 7.41 – 7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.33 – 5.30 (m, 1H), 4.75 (s, 1H), 4.58 (d, J = 8.2 Hz, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.2 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.16 (t, J = 7.0 Hz, 2H), 3.11 – 3.08 (m, 1H), 3.03 – 3.00 (m, 1H), 2.86 – 2.82 (m, 1H), 2.73 (dd, J = 14.0, 8.7 Hz, 1H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.11 (m, 9H), 1.96 (td, J = 9.1, 4.7 Hz, 1H), 1.76 – 1.73 (m, 2H), 1.59 (td, J = 10.5, 5.2 Hz, 4H), 1.49 – 1.45 (m, 2H), 1.35 – 1.27 (m, 10H), 1.17 (d, J = 13.1 Hz, 6H), 1.10 (s, 2H), 1.06 (s, 9H).HRMS (ESI) m/z: calcd for C₇₇H₉₆FN₁₀O₇S⁺ [M + H]⁺, 1323.7163; found, 1323.6869. Example 38 Synthesis of NS113-054

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((12-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)dodecyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-054 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-((S)- 3-((12-aminododecyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)-1-(2- (1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine- 2-carboxamide. (white solid, 11.0 mg, 41%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.46 – 7.42 (m, 4H), 7.41 – 7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.6, 5.7 Hz, 1H), 4.74 (d, J = 9.3 Hz, 1H), 4.58 (d, J = 8.3 Hz, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.17 (d, J = 7.0 Hz, 2H), 3.11 – 3.08 (m, 1H), 3.03 – 3.00 (m, 1H), 2.86 – 2.82 (m, 1H), 2.75 – 2.72 (m, 1H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.12 (m, 9H), 1.98 – 1.94 (m, 1H), 1.77 – 1.73 (m, 2H), 1.59 (dd, J = 13.2, 5.8 Hz, 4H), 1.49 (d, J = 7.2 Hz, 2H), 1.34 – 1.27 (m, 12H), 1.17 (s, 6H), 1.10 (s, 2H), 1.06 (s, 9H).HRMS (ESI) m/z: calcd for C₇₈H₉₈FN₁₀O₇S⁺ [M + H]⁺, 1337.7319; found, 1337.7030. Example 39 Synthesis of NS113-055

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((2-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)ethyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-055 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((2- aminoethyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 8.5 mg, 35%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.40 – 7.37 (m, 4H), 7.34 – 7.32 (m, 2H), 7.30 (s, 1H), 7.15 (d, J = 6.1 Hz, 1H), 7.13 – 7.11 (m, 2H), 7.08 – 7.05 (m, 2H), 6.92 (d, J = 1.6 Hz, 1H), 6.87 (s, 1H), 6.75 (d, J = 7.7 Hz, 1H), 5.43 (s, 2H), 4.72 (d, J = 9.2 Hz, 1H), 4.63 – 4.58 (m, 3H), 4.55 (d, J = 14.8 Hz, 1H), 4.48 (s, 1H), 4.44 (d, J = 14.9 Hz, 2H), 3.84 (d, J = 11.1 Hz, 1H), 3.79 – 3.74 (m, 2H), 3.45 – 3.39 (m, 4H), 2.45 (s, 3H), 2.44 – 2.39 (m, 2H), 2.35 (t, J = 7.0 Hz, 2H), 2.19-2.15 (m, 8H), 1.71 (d, J = 7.8 Hz, 2H), 1.62 – 1.54 (m, 4H), 1.35 – 1.30 (m, 4H), 0.98 (s, 9H).HRMS (ESI) m/z: calcd for C₆₈H₇₈FN₁₀O₈S⁺ [M + H]⁺, 1213.5703; found, 1213.5476. Example 40 Synthesis of NS113-056

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((3-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)propyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-056 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2- (2-((3-aminopropyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2- (1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine- 2-carboxamide. (white solid, 8.6 mg, 35%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.47 (dd, J = 8.5, 3.4 Hz, 1H), 7.40 – 7.37 (m, 4H), 7.35 – 7.33 (m, 3H), 7.32 – 7.30 (m, 1H), 7.20-7.16 (m, 1H), 7.15 – 7.13 (m, 2H), 7.11 – 7.07 (m, 2H), 6.96 (d, J = 1.6 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.77 (d, J = 9.0 Hz, 1H), 5.44 (s, 2H), 4.73 – 4.71 (m, 1H), 4.64 – 4.54 (m, 4H), 4.49 – 4.42 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.79-3.75 (m, 2H), 3.33 (d, J = 6.3 Hz, 2H), 3.19 (t, J = 6.7 Hz, 2H), 2.47 (s, 3H), 2.44 – 2.37 (m, 4H), 2.21 – 2.11 (m, 8H), 1.77 – 1.71 (m, 4H), 1.62 – 1.56 (m, 4H), 1.36 – 1.26 (m, 4H), 1.00 (s, 9H)..HRMS (ESI) m/z: calcd for C₆₉H₈₀FN₁₀O₈S⁺ [M + H]⁺, 1227.5860; found, 1227.6262. Example 41 Synthesis of NS113-057

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((4-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)butyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-057 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((4- aminobutyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 7.9 mg, 32%) ¹H NMR (600 MHz, Methanol-d4) δ 8.91 (s, 1H), 8.71 (s, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.39-7.35 (m, 4H), 7.34-7.31 (m, 4H), 7.19 – 7.17 (m, 1H), 7.17-7.12 (m, 2H), 7.11 – 7.07 (m, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.86 (d, J = 1.9 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 5.44 (s, 2H), 4.73 (d, J = 9.3 Hz, 1H), 4.64 – 4.54 (m, 4H), 4.50 – 4.41 (m, 3H), 3.83 (s, 1H), 3.79 – 3.73 (m, 2H), 3.29 (s, 2H), 3.17 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.45 – 2.33 (m, 4H), 2.23 – 2.12 (m, 8H), 1.76- 1.72 (m, 2H), 1.64 – 1.47 (m, 8H), 1.36 – 1.26 (m, 4H), 1.00 (s, 9H). HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₈S⁺ [M + H]⁺, 1241.6016; found, 1241.2350. Example 42 Synthesis of NS113-058

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((5-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)pentyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-058 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((5- aminopentyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 8.6 mg, 34%) ¹H NMR (600 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.71 (s, 1H), 7.48 (d, J = 7.7 Hz, 2H), 7.39-7.36 (m, 4H), 7.34 – 7.33 (m, 2H), 7.31 (s, 1H), 7.19 – 7.16 (m, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.07 (m, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 2.0 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.74 – 4.71 (m, 1H), 4.61 – 4.55 (m, 4H), 4.44 (d, J = 14.9 Hz, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.79 – 3.74 (m, 2H), 3.30 – 3.26 (m, 2H), 3.13 (t, J = 7.0 Hz, 2H), 2.47 (s, 3H), 2.38 (t, J = 7.0 Hz, 2H), 2.22 – 2.11 (m, 10H), 1.75-1.70 (m, 2H), 1.63 – 1.55 (m, 6H), 1.52 – 1.47 (m, 2H), 1.36 – 1.28 (m, 6H), 1.00 (s, 9H).HRMS (ESI) m/z: calcd for C₇₁H₈₄FN₁₀O₈S⁺ [M + H]⁺, 1255.6173; found, 1255.6827. Example 43 Synthesis of NS113-059

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((6-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)hexyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-059 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((6- aminohexyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 8.3 mg, 33%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.47 (t, J = 7.7 Hz, 2H), 7.39-7.36 (m, 4H), 7.35 – 7.33 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.18 (dt, J = 7.7, 1.4 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.07 (m, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.73 (d, J = 9.3 Hz, 1H), 4.61 – 4.55 (m, 4H), 4.49 – 4.43 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.80 – 3.74 (m, 2H), 3.26 (dd, J = 7.1, 4.0 Hz, 2H), 3.13 (t, J = 7.0 Hz, 2H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.08 (m, 10H), 1.74 (dd, J = 9.0, 6.3 Hz, 2H), 1.62 – 1.53 (m, 6H), 1.44 (d, J = 7.0 Hz, 2H), 1.36 – 1.28 (m, 8H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₂H₈₆FN₁₀O₈S⁺ [M + H]⁺, 1269.6329; found, 1269.7416. Example 44 Synthesis of NS113-060

( S, ) ((S) ( uo ocyc op opa e ca bo a do) 3,3 d et y buta oyl)- 4-hydroxy-N-(2-(2-((7-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)heptyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-060 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((7- aminoheptyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 9.3 mg, 36%) ¹H NMR (600 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.48 (d, J = 7.7 Hz, 2H), 7.39-7.36 (m, 4H), 7.35 – 7.33 (m, 2H), 7.31 (d, J = 7.4 Hz, 1H), 7.19 – 7.16 (m, 1H), 7.15 – 7.13 (m, 2H), 7.11 – 7.08 (m, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.44 (s, 2H), 4.74 – 4.72 (m, 1H), 4.61 – 4.56 (m, 4H), 4.49 – 4.42 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.80 – 3.75 (m, 2H), 3.26 (p, J = 3.5 Hz, 2H), 3.14 (t, J = 7.0 Hz, 2H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.23 – 2.09 (m, 10H), 1.74 (dd, J = 9.0, 6.3 Hz, 2H), 1.61 – 1.53 (m, 6H), 1.46 (t, J = 6.9 Hz, 2H), 1.35 – 1.26 (m, 10H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₃H₈₈FN₁₀O₈S⁺ [M + H]⁺, 1283.6486; found, 1283.7125. Example 45 Synthesis of NS113-061

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((8-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hept-6- ynamido)octyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine- 2-carboxamide. NS113-061 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and (2S,4R)-N-(2-(2-((8- aminooctyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2- carboxamide. (white solid, 8.9 mg, 34%) ¹H NMR (600 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.71 (s, 1H), 7.48 (t, J = 7.4 Hz, 2H), 7.41-7.38 (m, 4H), 7.35 – 7.33 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.19 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 – 7.08 (m, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.73 (d, J = 9.3 Hz, 1H), 4.61 – 4.57 (m, 4H), 4.44 (d, J = 14.9 Hz, 3H), 3.85 (s, 1H), 3.79 – 3.75 (m, 2H), 3.28 – 3.24 (m, 2H), 3.14 (t, J = 7.0 Hz, 2H), 2.48 (s, 3H), 2.39 (t, J = 7.0 Hz, 2H), 2.22 – 2.08 (m, 10H), 1.77 – 1.73 (m, 2H), 1.59 (dd, J = 14.5, 7.1 Hz, 4H), 1.52-1.46 (m, 4H), 1.36 – 1.26 (m, 12H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₄H₉₀FN₁₀O₈S⁺ [M + H]⁺, 1297.6642; found, 1297.8013. Example 46 Synthesis of NS106-051

2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide. NS106-051 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycine. (yellow solid, 9.2 mg, 52%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.71 (s, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.44 – 7.34 (m, 4H), 7.32 (t, J = 7.9 Hz, 4H), 7.17-7.11 (m, 4H), 7.02 (d, J = 7.2 Hz, 1H), 6.88 (s, 1H), 6.84 (d, J = 8.5 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.06 (dd, J = 12.7, 5.5 Hz, 1H), 4.43 (d, J = 13.2 Hz, 1H), 3.98 (s, 2H), 3.75 (s, 1H), 3.27 (t, J = 8.6 Hz, 2H), 2.86 – 2.81 (m, 1H), 2.74-2.71 (m, 2H), 2.36 (t, J = 7.1 Hz, 2H), 2.21 – 2.03 (m, 7H), 1.68 – 1.57 (m, 4H), 1.52 (t, J = 7.6 Hz, 2H). HRMS (ESI) m/z: calcd for C₅₂H₅₁N₈O₆ ⁺ [M + H]⁺, 883.3926; found, 883.3160. Example 47 Synthesis of NS106-052

3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)propanamide. NS106-052 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)propanoic acid. (yellow solid, 9.3 mg, 52%) ¹H NMR (800 MHz, Methanol- d4) δ 8.70 (s, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.39 (d, J = 7.1 Hz, 4H), 7.35 – 7.26 (m, 4H), 7.15 (d, J = 7.6 Hz, 3H), 7.11-7.06 (m, 2H), 6.98 (d, J = 7.1 Hz, 1H), 6.87 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.98 (dd, J = 12.2, 5.2 Hz, 1H), 4.44 – 4.39 (m, 1H), 3.73 (d, J = 11.0 Hz, 1H), 3.63 (t, J = 6.2 Hz, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.71 – 2.63 (m, 3H), 2.51 (t, J = 6.3 Hz, 2H), 2.32 (t, J = 7.0 Hz, 2H), 2.18 – 2.00 (m, 7H), 1.60 – 1.44 (m, 6H). HRMS (ESI) m/z: calcd for C53H53N8O6⁺ [M + H]⁺, 897.4083; found, 897.3151. Example 48 Synthesis of NS106-053

4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)butanamide. NS106-053 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)butanoic acid. (yellow solid, 9.0 mg, 49%) ¹H NMR (800 MHz, Methanol- d₄) δ 8.70 (s, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 6.1 Hz, 4H), 7.32 (d, J = 7.6 Hz, 4H), 7.18-7.12 (m, 3H), 7.08 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H), 6.95 (d, J = 7.0 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.43 (s, 2H), 5.05 – 5.01 (m, 1H), 4.42 (s, 1H), 3.75 (s, 1H), 3.35 (d, J = 6.3 Hz, 2H), 3.22 (d, J = 6.6 Hz, 2H), 2.81 (d, J = 15.4 Hz, 1H), 2.72-2.67 (m, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.30 (t, J = 7.2 Hz, 2H), 2.21 – 2.04 (m, 7H), 1.97 – 1.92 (m, 2H), 1.67 – 1.52 (m, 6H). HRMS (ESI) m/z: calcd for C₅₄H₅₅N₈O₆ ⁺ [M + H]⁺, 911.4239; found, 911.4142. Example 49 Synthesis of NS106-054

5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)pentanamide. NS106-054 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)pentanoic acid. (yellow solid, 9.5 mg, 51%) ¹H NMR (800 MHz, Methanol- d4) δ 8.70 (s, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 6.4 Hz, 4H), 7.32 (d, J = 7.1 Hz, 4H), 7.18-7.13 (m, 4H), 6.98 (t, J = 6.6 Hz, 2H), 6.86 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 5.43 (s, 2H), 5.04 – 5.00 (m, 1H), 4.42 (s, 1H), 3.75 (s, 1H), 3.22 (d, J = 6.6 Hz, 2H), 2.81 (d, J = 13.7 Hz, 1H), 2.72 – 2.66 (m, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.24 (t, J = 7.4 Hz, 2H), 2.21 – 1.99 (m, 9H), 1.75 – 1.54 (m, 10H). HRMS (ESI) m/z: calcd for C55H57N8O6⁺ [M + H]⁺, 925.4396; found, 925.3135. Example 50 Synthesis of NS106-055

6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)hexanamide. NS106-055 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)hexanoic acid. (yellow solid, 9.8 mg, 52%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.65 (d, J = 8.6 Hz, 1H), 7.56 (s, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 7.1 Hz, 3H), 7.32 (t, J = 7.6 Hz, 3H), 7.19 – 7.07 (m, 4H), 6.97 (dd, J = 14.9, 7.8 Hz, 2H), 6.85 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.42 (s, 2H), 5.03 (dd, J = 14.5, 6.0 Hz, 1H), 4.45 – 4.40 (m, 1H), 3.75 (s, 1H), 3.27 (t, J = 7.2 Hz, 2H), 3.21 (t, J = 6.9 Hz, 2H), 2.85 – 2.79 (m, 1H), 2.70 (t, J = 14.2 Hz, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.22 – 2.05 (m, 9H), 1.67 – 1.56 (m, 8H), 1.43 (t, J = 7.9 Hz, 2H). HRMS (ESI) m/z: calcd for C56H59N8O6⁺ [M + H]⁺, 939.4552; found, 939.4130. Example 51 Synthesis of NS106-056

7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)heptanamide. NS106-056 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)heptanoic acid. (yellow solid, 9.8 mg, 51%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 6.6 Hz, 4H), 7.32 (d, J = 7.7 Hz, 4H), 7.15-7.11 (m, 4H), 6.99-6.94 (m, 2H), 6.85 (s, 1H), 6.77 (d, J = 7.9 Hz, 1H 5.43 (s, 2H), 5.03 (dd, J = 13.0, 5.6 Hz, 1H), 4.42 (t, J = 12.0 Hz, 1H), 3.75 (s, 1H), 3.25 (t, J = 7.1 Hz, 2H), 3.21 (t, J = 6.9 Hz, 2H), 2.85 – 2.80 (m, 1H), 2.75 – 2.67 (m, 2H), 2.38 (t, J = 7.0 Hz, 2H), 2.21 – 2.08 (m, 9H), 1.65 – 1.54 (m, 10H), 1.42 – 1.37 (m, 2H). HRMS (ESI) m/z: calcd for C₅₇H₆₁N₈O₆ ⁺ [M + H]⁺, 953.4709; found, 953.6126. Example 52 Synthesis of NS106-057

¹⁰ 3-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)-N-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)propanamide. NS106- 057 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)propanoic acid. (yellow solid, 8.7 mg, 46%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.69 (s, 1H), 7.46 (s, 1H), 7.38 (d, J = 6.6 Hz, 4H), 7.33 (d, J = 7.3 Hz, 4H), 7.15 (dd, J = 17.1, 7.6 Hz, 3H), 7.09 (d, J = 7.8 Hz, 1H), 7.03-6.97 (m, 2H), 6.86 (s, 1H), 6.76 (d, J = 7.9 Hz, 1H), 5.43 (s, 2H), 5.02 (dd, J = 13.2, 4.8 Hz, 1H), 4.45 – 4.39 (m, 1H), 3.75 (t, J = 6.0 Hz, 3H), 3.66 (t, J = 5.4 Hz, 2H), 3.45 (t, J = 5.4 Hz, 2H), 3.20 (t, J = 6.7 Hz, 2H), 2.79 (t, J = 14.8 Hz, 1H), 2.68 (d, J = 14.8 Hz, 2H), 2.44 (t, J = 5.9 Hz, 2H), 2.34 (t, J = 6.9 Hz, 2H), 2.12 (ddd, J = 57.0, 31.7, 10.1 Hz, 7H), 1.63 – 1.54 (m, 6H). HRMS (ESI) m/z: calcd for C₅₅H₅₇N₈O₇ ⁺ [M + H]⁺, 941.4345; found, 941.3129. Example 53 Synthesis of NS106-058 3-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethoxy)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)propanamide. NS106-058 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-(2-((2-(2,6-dioxopiperidin-3-yl)- 1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)propanoic acid. (yellow solid, 9.0 mg, 46%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.6 Hz, 4H), 7.33 (d, J = 7.2 Hz, 4H), 7.19 – 7.06 (m, 4H), 7.01 (t, J = 6.9 Hz, 2H), 6.86 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.43 (s, 2H), 5.02 (dd, J = 12.5, 5.5 Hz, 1H), 4.44 – 4.39 (m, 1H), 3.78 – 3.70 (m, 3H), 3.67 (d, J = 5.6 Hz, 2H), 3.61 (d, J = 9.8 Hz, 4H), 3.42 (d, J = 5.7 Hz, 2H), 3.19 (t, J = 6.9 Hz, 2H), 2.83 – 2.78 (m, 1H), 2.69 (t, J = 16.6 Hz, 2H), 2.41 (t, J = 6.1 Hz, 2H), 2.35 (t, J = 7.0 Hz, 2H), 2.21 – 2.04 (m, 7H), 1.65 – 1.51 (m, 6H).HRMS (ESI) m/z: calcd for C₅₇H₆₁N₈O₈ ⁺ [M + H]⁺, 985.4607; found, 985.3126. Example 54 Synthesis of NS106-059

3-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethoxy)ethoxy)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)propanamide. NS106-059 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3- (2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4- yl)amino)ethoxy)ethoxy)ethoxy)propanoic acid. (yellow solid, 10.0 mg, 49%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.5 Hz, 4H), 7.32 (t, J = 7.7 Hz, 4H), 7.16-7.12 (m, 4H), 7.04 (d, J = 8.6 Hz, 1H), 7.02 (d, J = 7.0 Hz, 1H), 6.87 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 12.8, 5.1 Hz, 1H), 4.42 (t, J = 12.0 Hz, 1H), 3.76 – 3.73 (m, 1H), 3.71-3.66 (m, 4H), 3.61 (s, 4H), 3.60 (q, J = 3.8 Hz, 2H), 3.57 (q, J = 4.1 Hz, 2H), 3.46 (t, J = 5.2 Hz, 2H), 3.21 (t, J = 6.8 Hz, 2H), 2.84 – 2.79 (m, 1H), 2.70 (t, J = 16.1 Hz, 2H), 2.39 (dt, J = 21.5, 6.4 Hz, 4H), 2.19 – 2.06 (m, 7H), 1.64 – 1.54 (m, 6H). HRMS (ESI) m/z: calcd for C₅₉H₆₅N₈O₉+ [M + H]⁺, 1029.4869; found, 1029.3647. Example 55 Synthesis of NS106-060

((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12-tetraoxapentadecan-15- amide. NS106-060 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 1-((2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxapentadecan-15-oic acid. (yellow solid, 9.7 mg, 45%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.70 (d, J = 3.8 Hz, 1H), 7.51 (d, J = 7.3 Hz, 1H), 7.39 (d, J = 6.4 Hz, 4H), 7.33 (d, J = 7.5 Hz, 4H), 7.18-7.13 (m, 4H), 7.05-7.01 (m, 2H), 6.87 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 5.44 (d, J = 3.7 Hz, 2H), 5.02 (dd, J = 12.0, 6.0 Hz, 1H), 4.41 (d, J = 13.8 Hz, 1H), 3.75 (s, 1H), 3.69 (q, J = 4.8, 4.2 Hz, 4H), 3.65 – 3.52 (m, 10H), 3.47 (d, J = 5.3 Hz, 2H), 3.35 (d, J = 3.8 Hz, 2H), 3.23 – 3.17 (m, 2H), 2.81 (d, J = 16.4 Hz, 1H), 2.70 (t, J = 17.7 Hz, 2H), 2.44-2.36 (m, 4H), 2.17-2.12 (m, 7H), 1.68 – 1.53 (m, 6H). HRMS (ESI) m/z: calcd for C₆₁H₆₉N₈O₁₀ ⁺ [M + H]⁺, 1073.5131; found, 1073.4202. Example 56 Synthesis of NS106-061

1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12,15-pentaoxaoctadecan- NS106-033 from Intermediate 2 and 1-((2-(2,6-dioxopiperidin-3-yl)-1,3- dioxoisoindolin-4-yl)amino)-3,6,9,12,15-pentaoxaoctadecan-18-oic acid. (yellow solid, 9.3 mg, 42%) ¹H NMR (800 MHz, Methanol-d4) δ 8.70 (s, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 6.5 Hz, 4H), 7.32 (t, J = 7.8 Hz, 4H), 7.20 – 7.09 (m, 4H), 7.06 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 7.1 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 5.03 (dd, J = 13.2, 4.9 Hz, 1H), 4.42 (t, J = 12.0 Hz, 1H), 3.75 (t, J = 10.7 Hz, 1H), 3.70 (q, J = 5.7, 4.9 Hz, 4H), 3.66 – 3.60 (m, 6H), 3.60 – 3.49 (m, 10H), 3.47 (t, J = 5.2 Hz, 2H), 3.22 (t, J = 6.7 Hz, 2H), 2.85 – 2.81 (m, 1H), 2.73-2.68 (m, 2H), 2.42-2.37 (m, 4H), 2.19 – 2.07 (m, 7H), 1.63-1.58 (m, 6H). HRMS (ESI) m/z: calcd for C₆₃H₇₃N₈O₁₁+ [M + H]⁺, 1117.5393; found, 1117.1794. Example 57 Synthesis of NS106-078

2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide. NS106-078 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycine. (yellow solid, 8.7 mg, 49%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.39 (d, J = 7.0 Hz, 4H), 7.36 – 7.27 (m, 4H), 7.14 (d, J = 7.8 Hz, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.97 (s, 1H), 6.86 (s, 1H), 6.84 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.99 (dd, J = 12.8, 5.5 Hz, 1H), 4.45 – 4.40 (m, 1H), 3.90 (s, 2H), 3.77 – 3.72 (m, 1H), 3.27 (d, J = 6.0 Hz, 2H), 2.79-2.74 (m, 1H), 2.69 – 2.60 (m, 2H), 2.33 (t, J = 7.0 Hz, 2H), 2.19 – 2.09 (m, 6H), 2.01 – 1.97 (m, 1H), 1.64 – 1.56 (m, 4H), 1.53 – 1.49 (m, 2H). HRMS (ESI) m/z: calcd for C₅₂H₅₁N₈O₆ ⁺ [M + H]⁺, 883.3926; found, 883.3660. Example 58 Synthesis of NS113-176

N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-2-((2-(1-methyl-2,6- dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamide. NS113-176 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (2-(1-methyl-2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)glycine. (yellow solid, 8.2 mg, 46%) ¹H NMR (600 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.67 – 7.63 (m, 2H), 7.58 – 7.54 (m, 2H), 7.40-7.36 (m, 3H), 7.34 – 7.30 (m, 3H), 7.14 (dd, J = 8.3, 1.4 Hz, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.98 (d, J = 2.2 Hz, 1H), 6.87 (s, 1H), 6.85 (dd, J = 8.3, 2.2 Hz, 1H), 6.77 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 5.02 (dd, J = 12.9, 5.4 Hz, 1H), 4.42 (t, J = 11.7 Hz, 1H), 3.90 (s, 2H), 3.77 – 3.73 (m, 1H), 3.27 (q, J = 6.4 Hz, 2H), 3.11 (s, 3H), 2.82 – 2.80 (m, 1H), 2.63-2.57 (m, 1H), 2.34 (t, J = 7.0 Hz, 2H), 2.20 – 2.06 (m, 7H), 2.01 – 1.96 (m, 1H), 1.64 – 1.56 (m, 4H), 1.54-1.49 (m, 2H). HRMS (ESI) m/z: calcd for C₅₃H₅₃N₈O₆ ⁺ [M + H]⁺, 897.4083; found, 897.5746. Example 59 Synthesis of NS106-079

3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)propanamide. NS106-079 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)propanoic acid. (yellow solid, 8.4 mg, 47%) ¹H NMR (800 MHz, Methanol- d4) δ 8.70 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 6.1 Hz, 4H), 7.32 (q, J = 7.6, 7.0 Hz, 4H), 7.14 (td, J = 27.1, 26.3, 7.7 Hz, 4H), 7.00 (s, 1H), 6.88 (s, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.01 (dd, J = 12.8, 5.5 Hz, 1H), 4.44 – 4.40 (m, 1H), 3.77 – 3.72 (m, 1H), 3.53 (t, J = 6.7 Hz, 2H), 3.21 (t, J = 6.8 Hz, 2H), 2.85 – 2.80 (m, 1H), 2.72 – 2.64 (m, 2H), 2.50 (t, J = 6.7 Hz, 2H), 2.35 (d, J = 7.0 Hz, 2H), 2.18-2.15 (m, 4H), 2.13 – 2.08 (m, 2H), 2.06-2.01 (m, 1H), 1.62 – 1.57 (m, 4H), 1.55 – 1.51 (m, 2H). HRMS (ESI) m/z: calcd for C₅₃H₅₃N₈O₆ ⁺ [M + H]⁺, 897.4083; found, 897.4028. Example 60 Synthesis of NS106-096

4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)butanamide. NS106-096 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)butanoic acid. (yellow solid, 8.3 mg, 46%) ¹H NMR (600 MHz, Methanol-d₄) δ 870 (s 1H) 749 (d J = 84 Hz 1H) 740 – 736 (m 4H) 734 – 730 (m 4H) 716 (dt, J = 7.8, 1.5 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.08 (t, J = 7.7 Hz, 1H), 6.95 (d, J = 2.2 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.80 (dd, J = 8.4, 2.2 Hz, 1H), 6.76 (dt, J = 7.8, 1.5 Hz, 1H), 5.43 (s, 2H), 5.01 (dd, J = 12.8, 5.5 Hz, 1H), 4.45 – 4.39 (m, 1H), 3.78 – 3.72 (m, 1H), 3.25-3.21 (m, 4H), 2.85-2.80 (m, 1H), 2.74 – 2.64 (m, 2H), 2.38 (t, J = 6.8 Hz, 2H), 2.31 (t, J = 7.2 Hz, 2H), 2.21 – 2.14 (m, 4H), 2.14-2.08 (m, 2H), 2.06 – 2.02 (m, 1H), 1.97-1.93 (m, 2H), 1.66 – 1.55 (m, 6H). HRMS (ESI) m/z: calcd for C₅₄H₅₅N₈O₆ + [M + H]⁺, 911.4239; found, 911.4155. Example 61 Synthesis of NS106-080

5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)pentanamide. NS106-080 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 5-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)pentanoic acid. (yellow solid, 9.3 mg, 50%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.38 (d, J = 7.2 Hz, 4H), 7.32 (d, J = 6.9 Hz, 4H), 7.15-7.11 (m, 4H), 6.92 (s, 1H), 6.86 (s, 1H), 6.77 (t, J = 9.2 Hz, 2H), 5.43 (s, 2H), 5.03 – 4.99 (m, 1H), 4.44 – 4.40 (m, 1H), 3.75 (q, J = 8.5, 6.9 Hz, 1H), 3.22 (t, J = 6.8 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 2.85 – 2.79 (m, 1H), 2.72 – 2.65 (m, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.24 (t, J = 7.2 Hz, 2H), 2.16 (d, J = 17.1 Hz, 4H), 2.14 – 2.09 (m, 2H), 2.06 – 2.02 (m, 1H), 1.73 (t, J = 7.7 Hz, 2H), 1.67-1.62 (m, 4H), 1.60-1.55 (m, 4H). HRMS (ESI) m/z: calcd for C₅₅H₅₇N₈O₆ ⁺ [M + H]⁺, 925.4396; found, 925.4135. Example 62 Synthesis of NS106-081

((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)hexanamide. NS106-081 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)hexanoic acid. (yellow solid, 8.9 mg, 47%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.38 (d, J = 7.0 Hz, 4H), 7.32 (t, J = 7.5 Hz, 4H), 7.15-7.11 (m, 4H), 6.92 (s, 1H), 6.86 (s, 1H), 6.78 – 6.75 (m, 2H), 5.42 (s, 2H), 5.01 (dd, J = 12.8, 5.5 Hz, 1H), 4.45 – 4.41 (m, 1H), 3.75 (m, 1H), 3.24-3.18 (t, J = 6.8 Hz, 2H), 3.16 (t, J = 7.0 Hz, 2H), 2.83-2.77 (m, 1H), 2.72 – 2.66 (m, 2H), 2.37 (t, J = 6.9 Hz, 2H), 2.22-2.17 (m, 6H), 2.13 – 2.09 (m, 2H), 2.04 (d, J = 12.7 Hz, 1H), 1.66- 1.62 (m, 6H), 1.61-1.56 (m, 4H), 1.46 – 1.42 (m, 2H). HRMS (ESI) m/z: calcd for C₅₆H₅₉N₈O₆ ⁺ [M + H]⁺, 939.4552; found, 939.4916. Example 63 Synthesis of NS106-082

7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)heptanamide. NS106-082 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)heptanoic acid. (yellow solid, 10.0 mg, 52%) ¹H NMR (800 MHz, Methanol- d4) δ 8.69 (s, 1H), 7.49 (t, J = 8.6 Hz, 1H), 7.38 (t, J = 7.9 Hz, 4H), 7.31 (d, J = 8.4 Hz, 4H), 7.15-7.11 (m, 4H), 6.90 (d, J = 9.7 Hz, 1H), 6.85 (d, J = 9.8 Hz, 1H), 6.76 (d, J = 10.5 Hz, 2H), 5.42 (d, J = 9.3 Hz, 2H), 5.01 (s, 1H), 4.44 – 4.38 (m, 1H), 3.78 – 3.73 (m, 1H), 3.21 (q, J = 7.1 Hz, 2H), 3.15 – 3.10 (m, 2H), 2.83-2.78 (m, 1H), 2.74 – 2.67 (m, 2H), 2.37 (q, J = 7.3 Hz, 2H), 2.24 – 2.09 (m, 9H), 1.71 – 1.57 (m, 10H), 1.43 – 1.34 (m, 4H). HRMS (ESI) m/z: calcd for C₅₇H₆₁N₈O₆ ⁺ [M + H]⁺, 953.4709; found, 953.4817. Example 64 Synthesis of NS106-083

8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)octanamide. NS106-083 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5- yl)amino)octanoic acid. (yellow solid, 8.5 mg, 44%) ¹H NMR (800 MHz, Methanol-d4) δ 8.69 (s, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.38 (d, J = 6.9 Hz, 4H), 7.34 – 7.29 (m, 4H), 718 (d J = 77 Hz 1H) 713 (d J = 77 Hz 2H) 710 (t J = 77 Hz 1H) 691 (s 1H) 6.86 (s, 1H), 6.79-6.75 (m, 2H), 5.43 (s, 2H), 5.01 (dd, J = 12.4, 5.7 Hz, 1H), 4.45-4.41 (m, 1H), 3.77-3.73 (m, 1H), 3.21 (t, J = 6.7 Hz, 2H), 3.12 (t, J = 7.1 Hz, 2H), 2.84 – 2.80 (m, 1H), 2.73 – 2.67 (m, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.20 – 2.14 (m, 6H), 2.12 – 2.08 (m, 2H), 2.07 – 2.03 (m, 1H), 1.63-1.60 (m, 10H), 1.42 – 1.34 (m, 6H). HRMS (ESI) m/z: calcd for C₅₈H₆₃N₈O₆ ⁺ [M + H]⁺, 967.4865; found, 967.5077. Example 65 Synthesis of NS106-111

6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-N-(6-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)hex-5-ynamide. NS106-111 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-ynoic acid. (yellow solid, 6.2 mg, 34%) ¹H NMR (600 MHz, Methanol-d4) δ 8.70 (s, 1H), 7.73 – 7.70 (m, 1H), 7.58 (dd, J = 7.7, 1.0 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.40 – 7.36 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 (d, J = 7.7 Hz, 1H), 6.85 (d, J = 1.9 Hz, 1H), 6.77 (d, J = 7.7 Hz, 1H), 5.43 (s, 2H), 5.15 (dd, J = 13.4, 5.2 Hz, 1H), 4.49 (s, 1H), 4.47 (s, 1H), 4.43 (s, 1H), 3.76 (d, J = 4.3 Hz, 1H), 3.21 (t, J = 6.5 Hz, 2H), 2.88 (dd, J = 5.5, 4.0 Hz, 1H), 2.78 – 2.74 (m, 1H), 2.54 – 2.47 (m, 3H), 2.37 (t, J = 7.0 Hz, 3H), 2.20 – 2.09 (m, 8H), 1.95 – 1.91 (m, 2H), 1.65 – 1.56 (m, 6H). HRMS (ESI) m/z: calcd for C56H56N7O5 ⁺ [M + H]⁺, 906.4337; found, 906.4513. Example 66 Synthesis of NS113-168

3-(4-(5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)amino)pent-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione. Intermediate 2 (11.4 mg, 0.02 mmol, 1 equiv), 5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4- yl)pent-4-yn-1-yl methanesulfonate (12.1 mg, 0.03 mmol, 1.5 equiv), DIPEA (12 mg, 0.09 mmol, 4.5 equiv), NaI (9 mg, 0.06 mmol, 3 equiv) in NMP (1 mL). NS113-168 was purified by pre-HPLC. (yellow solid, 5.2 mg, 20%) ¹H NMR (600 MHz, Methanol- d4) δ 8.70 (s, 1H), 7.75 (dd, J = 7.6, 1.0 Hz, 1H), 7.62 (dd, J = 7.6, 1.0 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.41-7.36 (m, 4H), 7.34 – 7.31 (m, 4H), 7.20 – 7.18 (m, 1H), 7.14 – 7.11 (m, 3H), 6.86 (s, 1H), 6.79 (d, J = 6.3 Hz, 1H), 5.44 (s, 2H), 5.18 (dd, J = 13.3, 5.2 Hz, 1H), 4.50 (s, 1H), 4.47 (d, J = 7.6 Hz, 1H), 4.44 – 4.42 (m, 1H), 3.73 (d, J = 7.1 Hz, 2H), 3.40 (t, J = 7.4 Hz, 1H), 3.01 (d, J = 8.1 Hz, 1H), 2.94 – 2.89 (m, 1H), 2.80 – 2.77 (m, 1H), 2.66 (t, J = 6.9 Hz, 2H), 2.46 (q, J = 6.8 Hz, 3H), 2.19 – 2.11 (m, 8H), 2.03 – 1.99 (m, 2H), 1.69 – 1.58 (m, 6H). HRMS (ESI) m/z: calcd for C₅₅H₅₆N₇O₄ ⁺ [M + H]⁺, 878.4388; found, 878.6754. Example 67 Synthesis of NS106-065

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N4-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)succinamide. NS106- 065 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 4-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4- oxobutanoic acid. (white solid, 10.2 mg, 47%) ¹H NMR (800 MHz, Methanol-d4) δ 8.88 (s, 1H), 8.72 (s, 1H), 7.49 – 7.28 (m, 12H), 7.19 – 7.09 (m, 4H), 6.85 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.59 (s, 1H), 4.57 – 4.52 (m, 2H), 4.48 (s, 1H), 4.44 (d, J = 11.2 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.88 (d, J = 11.0 Hz, 1H), 3.79 – 3.74 (m, 2H), 3.22-3.17 (m, 2H), 2.61 (d, J = 7.1 Hz, 1H), 2.51 – 2.44 (m, 5H), 2.39 (t, J = 6.9 Hz, 2H), 2.21 – 2.06 (m, 9H), 1.65 – 1.57 (m, 6H), 1.01 (s, 9H). HRMS (ESI) m/z: calcd for C₆₃H₇₂N₉O₆S ⁺ [M + H]⁺, 1082.5321; found, 1082.5717. Example 68 Synthesis of NS106-066

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N5-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)glutaramide. NS106- 066 was synthesized following the standard procedure for preparing NS106-033 from yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5- oxopentanoic acid. (white solid, 9.7 mg, 44%) ¹H NMR (800 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.55 – 7.26 (m, 12H), 7.20 – 7.07 (m, 4H), 6.85 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.60 (s, 1H), 4.58 – 4.49 (m, 3H), 4.43 (s, 1H), 4.35 (d, J = 15.6 Hz, 1H), 3.91 (d, J = 10.9 Hz, 1H), 3.83-3.77 (m, 1H), 3.76 (s, 1H), 3.24 – 3.17 (m, 2H), 2.46 (s, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.31-2.26 (m, 3H), 2.23 – 2.10 (m, 9H), 1.91-1.87 (m, 2H), 1.67 – 1.56 (m, 6H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₆₄H₇₄N₉O₆S ⁺ [M + H]⁺, 1096.5477; found, 1096.4244. Example 69 Synthesis of NS106-067

N -((S)- -(( S, )- - ydroxy- -(( -( -met y t azo -5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N6-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)adipamide. NS106- 067 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6- oxohexanoic acid. (white solid, 9.8 mg, 44%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.49 – 7.25 (m, 12H), 7.21 – 7.08 (m, 4H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.62 (s, 1H), 4.58 – 4.48 (m, 3H), 4.44 (d, J = 4.5 Hz, 1H), 4.35 (d, J = 15.5 Hz, 1H), 3.89 (d, J = 10.9 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.21 (t, J = 7.0 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.29 – 2.09 (m, 12H), 1.60 (d, J = 22.8 Hz, 10H), 1.02 (s, 9H). HRMS (ESI) m/z: calcd for C65H76N9O6S ⁺ [M + H]⁺, 1110.5634; found, 1110.2278. Example 70 Synthesis of NS106-068

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N7-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)heptanediamide. NS106-068 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 7-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-7- oxoheptanoic acid. (white solid, 10.4 mg, 46%) ¹H NMR (800 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.52 – 7.27 (m, 12H), 7.21 – 7.09 (m, 4H), 6.85 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.48 (m, 3H), 4.43 (s, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 11.0 Hz, 1H), 3.82 – 3.74 (m, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.40 (t, J = 6.9 Hz, 2H), 2.27 – 2.09 (m, 12H), 1.63-1.58 (m, 6.8 Hz, 10H), 1.36 – 1.31 (m, 2H), 1.02 (s, 9H). HRMS (ESI) m/z: calcd for C₆₆H₇₈N₉O₆S ⁺ [M + H]⁺, 1124.5790; found, 1124.4813. Example 71 Synthesis of NS106-069

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N8-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)octanediamide. NS106-069 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 8-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8- oxooctanoic acid. (white solid, 9.6 mg, 42%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.48 – 7.30 (m, 12H), 7.19 – 7.10 (m, 4H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.57 – 4.48 (m, 3H), 4.43 (s, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 10.9 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.26 – 2.11 (m, 12H), 1.63 – 1.57 (m, 10H), 1.35 – 1.31 (m, 4H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₇H₈₀N₉O₆S ⁺ [M + H]⁺, 1138.5947; found, 1138.5150.

Example 72 Synthesis of NS106-070

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N9-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)nonanediamide. NS106-070 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 9-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-9- oxononanoic acid. (white solid, 10.2 mg, 44%) ¹H NMR (800 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.50 – 7.28 (m, 12H), 7.20 – 7.10 (m, 4H), 6.85 (s, 1H), 6.79 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.58 – 4.49 (m, 3H), 4.42 (d, J = 11.7 Hz, 1H), 4.36 (d, J = 15.3 Hz, 1H), 3.90 (d, J = 10.9 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.19-2.14 (m, 12H), 1.63 – 1.54 (m, 10H), 1.31 (d, J = 3.8 Hz, 6H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₈H₈₂N₉O₆S ⁺ [M + H]⁺, 1152.6103; found, 1152.3402. Example 73 Synthesis of NS113-149

N1-((S)-1-((2S,4R)-4-(benzyloxy)-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N9-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)nonanediamide. NS113-149 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 9-(((S)-1-((2S,4R)-4-(benzyloxy)-2-((4-(4-methylthiazol- 5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-9- oxononanoic acid. (white solid, 13.0 mg, 52%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.90 (s, 1H), 8.71 (s, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.44 – 7.36 (m, 6H), 7.36 – 7.27 (m, 8H), 7.26 – 7.23 (m, 1H), 7.19 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.70 (s, 1H), 4.58 (d, J = 11.6 Hz, 1H), 4.56 – 4.53 (m, 1H), 4.52 – 4.47 (m, 2H), 4.45 – 4.40 (m, 1H), 4.37 (d, J = 15.5 Hz, 1H), 4.28 (d, J = 11.8 Hz, 2H), 3.76 – 3.72 (m, 2H), 3.21 – 3.17 (m, 2H), 2.47 (s, 3H), 2.38 (t, J = 6.8 Hz, 3H), 2.29 – 2.22 (m, 2H), 2.22 – 2.07 (m, 10H), 1.63 – 1.53 (m, 9H), 1.27 (s, 6H), 1.04 (s, 9H). HRMS (ESI) m/z: calcd for C₇₅H₈₈N₉O₆S ⁺ [M + H]⁺, 1242.6573; found, 1242.7975. Example 74 Synthesis of NS106-071

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N10-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)decanediamide. NS106-071 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 10-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-10- oxodecanoic acid. (white solid, 9.7 mg, 42%) ¹H NMR (800 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.66 – 7.63 (m, 1H), 7.58 – 7.55 (m, 1H), 7.47 (d, J = 7.5 Hz, 2H), 7.42-7.37 (m, 5H), 7.35 – 7.31 (m, 3H), 7.21 – 7.09 (m, 4H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.57 – 4.49 (m, 3H), 4.43 (s, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 10.8 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.28 – 2.10 (m, 12H), 1.62-1.58 (m, 10H), 1.31 (d, J = 14.3 Hz, 8H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₉H₈₄N₉O₆S ⁺ [M + H]⁺, 1166.6260; found, 1166.9957. Example 75 Synthesis of NS106-072

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N11-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)undecanediamide. NS106-072 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 11-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11- oxoundecanoic acid. (white solid, 8.7 mg, 37%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.57 – 7.26 (m, 12H), 7.20 – 7.09 (m, 4H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 1H), 4.57 – 4.48 (m, 3H), 4.43 (t, J = 11.8 Hz, 1H), 4.36 (d, J = 15.4 Hz, 1H), 3.90 (d, J = 10.6 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.21 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.28 – 2.08 (m, 12H), 1.62-1.58 (m, 10H), 1.29 (s, 10H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₇₀H₈₆N₉O₆S ⁺ [M + H]⁺, 1180.6416; found, 1180.6016. Example 76 Synthesis of NS106-073

(2S,4R)-4-hydroxy-1-((S)-2-(2-(2-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)amino)-2-oxoethoxy)acetamido)-3,3- dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS106-073 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 2-(2-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-2- oxoethoxy)acetic acid. (white solid, 8.9 mg, 41%) ¹H NMR (800 MHz, Methanol-d₄) δ 8.89 (s, 1H), 8.71 (s, 1H), 7.48 – 7.27 (m, 12H), 7.20 – 7.07 (m, 4H), 6.85 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.70 (s, 1H), 4.59 – 4.55 (m, 2H), 4.50 (s, 1H), 4.43 (dd, J = 13.6, 9.9 Hz, 1H), 4.32 (d, J = 15.4 Hz, 1H), 4.12 (d, J = 3.2 Hz, 2H), 4.06 (d, J = 2.7 Hz, 2H), 3.89 (d, J = 11.0 Hz, 1H), 3.83-3.78 (m, 1H), 3.75 (t, J = 4.2 Hz, 1H), 3.29 (t, J = 6.6 Hz, 2H), 2.46 (s, 3H), 2.38 (t, J = 6.9 Hz, 2H), 2.24 – 2.10 (m, 8H), 1.70 – 1.65 (m, 2H), 1.62 – 1.56 (m, 4H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₃H₇₂N₉O₇S ⁺ [M + H]⁺, 1098.5270; found, 1098.4120. Example 77 Synthesis of NS106-074

(2S,4R)-4-hydroxy-1-((S)-2-(3-(3-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)amino)-3-oxopropoxy)propanamido)-3,3- dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS106-074 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 2 and 3-(3-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-3- oxopropoxy)propanoic acid. (white solid, 10.6 mg, 47%) ¹H NMR (800 MHz, Methanol-d4) δ 8.87 (s, 1H), 8.72 (s, 1H), 7.52 – 7.25 (m, 12H), 7.19 – 7.09 (m, 4H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.65 (s, 1H), 4.57 – 4.49 (m, 3H), 4.43 (s, 1H), 4.35 (d, J = 15.5 Hz, 1H), 3.88 (d, J = 11.1 Hz, 1H), 3.81 – 3.79 (m, 1H), 3.75 (s, 1H), 3.69 (q, J = 8.6, 6.3 Hz, 3H), 3.66 – 3.63 (m, 1H), 3.21 (d, J = 6.1 Hz, 2H), 2.52 (s, 2H), 2.47 – 2.45 (m, 3H), 2.43 (t, J = 6.3 Hz, 2H), 2.38 (t, J = 7.0 Hz, 2H), 2.22 – 2.07 (m, 8H), 1.65 – 1.55 (m, 6H), 1.02 (s, 9H). HRMS (ESI) m/z: calcd for C₆₅H₇₆N₉O₇S ⁺ [M + H]⁺, 1126.5583; found, 1126.2319. Example 78 Synthesis of NS113-093

(2S,4R)-1-((S)-2-(tert-butyl)-18-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-4,11- dioxo-6,9-dioxa-3,12-diazaoctadec-17-ynoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-093 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 2-(2-(2-(((S)-1- ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)- 3,3-dimethyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)ethoxy)acetic acid. (white solid, 10.9 mg, 48%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.70 (s, 1H), 7.47- 7.44 (m, 2H), 7.42 – 7.40 (m, 2H), 7.38 – 7.36 (m, 4H), 7.33– 7.30 (m, 4H), 7.17 (dd, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.11 (t, J = 7.7 Hz, 1H), 6.85(d, J = 1.8 Hz, 1H), 6.77 (dd, J = 7.7, 1.6 Hz, 1H), 5.44 (s, 2H), 4.72 – 4.68 (m, 1H), 4.57 – 4.53 (m, 2H), 4.48 (d, J = 3.8 Hz, 1H), 4.41 (dd, J = 11.6, 3.7 Hz, 1H), 4.33 (d, J = 15.5 Hz, 1H), 4.07 – 3.97 (m, 2H), 3.97 – 3.90 (m, 2H), 3.85 (d, J = 11.0 Hz, 1H), 3.80 – 3.74 (m, 2H), 3.71 – 3.65 (m, 4H), 3.28-3.24 (m, 2H), 2.46 (s, 3H), 2.37 (t, J = 6.9 Hz, 2H), 2.22 – 2.08 (m, 8H), 1.68 – 1.61 (m, 2H), 1.60 – 1.54 (m, 4H), 1.02 (s, 9H).HRMS (ESI) m/z: calcd for C₆₅H₇₆N₉O₈S ⁺ [M + H]⁺, 1142.5532; found, 1142.4508. Example 79 Synthesis of NS106-075 (2

S,4R)-1-((S)-2-(tert-butyl)-20-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-4,13- dioxo-7,10-dioxa-3,14-diazaicos-19-ynoyl)-4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS106-075 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-(3-(((S)-1- ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)- 3,3-dimethyl-1-oxobutan-2-yl)amino)-3-oxopropoxy)ethoxy)propanoic acid. (white solid, 10.8 mg, 46%) ¹H NMR (800 MHz, Methanol-d4) δ 8.90 (s, 1H), 8.72 (s, 1H), 7.50 – 7.26 (m, 12H), 7.20 – 7.08 (m, 4H), 6.86 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.65 (s, 1H), 4.58 – 4.48 (m, 3H), 4.45 – 4.41 (m, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.88 (d, J = 10.9 Hz, 1H), 3.82 – 3.74 (m, 2H), 3.71-3.68 (m, 4H), 3.59 – 3.54 (m, 4H), 3.22 (t, J = 6.8 Hz, 2H), 2.55-2.51 (m, 2H), 2.47 (s, 3H), 2.43 – 2.38 (m, 4H), 2.22 – 2.09 (m, 8H), 1.63-1.58 (m, 6H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₇H₈₀N₉O₈S ⁺ [M + H]⁺, 1170.5845; found, 1170.4471. Example 80 Synthesis of NS113-094

(2S,4R)-1-((S)-2-(tert-butyl)-21-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-4,14- dioxo-6,9,12-trioxa-3,15-diazahenicos-20-ynoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-094 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-13-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-14,14-dimethyl-11-oxo-3,6,9-trioxa-12- azapentadecanoic acid. (white solid, 11.2 mg, 47%) ¹H NMR (600 MHz, Methanol-d4) δ 8.93 (s, 1H), 8.71 (s, 1H), 7.46 (dd, J = 7.9, 5.6 Hz, 2H), 7.43 – 7.40 (m, 2H), 7.39 – 7.36 (m, 4H), 7.34 – 7.30 (m, 4H), 7.18 (dd, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.78 (dd, J = 7.7, 1.6 Hz, 1H), 5.45 (s, 2H), 4.72 – 4.69 (m, 1H), 4.58 – 4.53 (m, 2H), 4.49 (d, J = 3.8 Hz, 1H), 4.42 (dd, J = 11.6, 3.7 Hz, 1H), 4.34 (d, J = 15.5 Hz, 1H), 4.07 – 3.99 (m, 2H), 3.98 – 3.90 (m, 2H), 3.86 (d, J = 11.0 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.72 – 3.65 (m, 8H), 3.27 (dt, J = 8.7, 6.9 Hz, 2H), 2.47 (s, 3H), 2.39 (t, J = 6.9 Hz, 2H), 2.23 – 2.08 (m, 8H), 1.68 – 1.62 (m, 2H), 1.61 – 1.54 (m, 4H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₆₇H₈₀N₉O₉S ⁺ [M + H]⁺, 1186.5794; found, 1186.6177. Example 81 Synthesis of NS106-076

(2S,4R)-1-((S)-2-(tert-butyl)-23-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-4,16- dioxo-7,10,13-trioxa-3,17-diazatricos-22-ynoyl)-4-hydroxy-N-(4-(4-methylthiazol- 5-yl)benzyl)pyrrolidine-2-carboxamide. NS106-076 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-15-((2S,4R)- 4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)- 16,16-dimethyl-13-oxo-4,7,10-trioxa-14-azaheptadecanoic acid. (white solid, 11.4 mg, 47%) ¹H NMR (800 MHz, Methanol-d4) δ 8.92 (s, 1H), 8.72 (s, 1H), 7.48 – 7.32 (m, 12H), 7.20 – 7.10 (m, 4H), 6.86 (s, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.65 (s, 1H), 4.58 – 4.48 (m, 3H), 4.44 (d, J = 3.7 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.88 (d, J = 10.9 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.73 – 3.68 (m, 4H), 3.59-3.52 (m, 8H), 3.22 (s, 2H), 2.62 – 2.50 (m, 2H), 2.47 (s, 3H), 2.42-2.37 (m, 4H), 2.21 – 2.10 (m, 8H), 1.63 (s, 6H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₉H₈₄N₉O₉S ⁺ [M + H]⁺, 1214.6107; found, 1214.4185. Example 82 Synthesis of NS113-095

N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N16-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-4,7,10,13- tetraoxahexadecanediamide. NS113-095 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-18-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)- 19,19-dimethyl-16-oxo-4,7,10,13-tetraoxa-17-azaicosanoic acid. (white solid, 10.6 mg, 42%) ¹H NMR (600 MHz, Methanol-d4) δ 9.01 (s, 1H), 8.71 (s, 1H), 7.48 – 7.45 (m, 2H), 7.44 – 7.41 (m, 2H), 7.40-7.36 (m, 4H), 7.34 – 7.30 (m, 4H), 7.20 – 7.17 (m, 1H 7.15 – 7.13 (m, 2H), 7.11 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H), 5.45 (s, 2H), 4.69 (s, 1H), 4.59 – 4.53 (m, 2H), 4.50 (q, J = 2.3 Hz, 1H), 4.43 (d, J = 11.6 Hz, 1H), 4.36 (d, J = 15.6 Hz, 1H), 4.06 – 3.99 (m, 2H), 3.96 (s, 2H), 3.87 (d, J = 11.1 Hz, 1H), 3.80 (dd, J = 11.0, 3.8 Hz, 1H), 3.76 (d, J = 4.1 Hz, 1H), 3.69 – 3.59 (m, 16H), 3.29 (t, J = 6.9 Hz, 2H), 2.48 (s, 3H), 2.40 (t, J = 6.9 Hz, 2H), 2.25 – 2.08 (m, 8H), 1.70 – 1.65 (m, 2H), 1.62 – 1.55 (m, 4H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₇₁H₈₈N₉O₁₀S ⁺ [M + H]⁺, 1258.6369; found, 1258.6552. Example 83 Synthesis of NS113-096 N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N17-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12,15- pentaoxaheptadecanediamide. NS113-096 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-19-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)- 20,20-dimethyl-17-oxo-3,6,9,12,15-pentaoxa-18-azahenicosanoic acid. (white solid, 10.5 mg, 41%) ¹H NMR (600 MHz, Methanol-d4) $ 8.93 (s, 1H), 8.72 (s, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.43 – 7.41 (m, 2H), 7.40 – 7.35 (m, 4H), 7.33 – 7.29 (m, 5H), 7.16 – 7.14 (m, 2H), 7.09 (d, J = 2.7 Hz, 1H), 6.97 (s, 1H), 6.91 (d, J = 6.1 Hz, 1H), 5.56 (s, 2H), 4.75 (d, J = 15.4 Hz, 1H), 4.64 (s, 1H), 4.59 – 4.52 (m, 2H), 4.51 – 4.48 (m, 1H), 4.46 (dd, J = 11.6, 3.6 Hz, 1H), 4.37 (d, J = 15.5 Hz, 1H), 4.25 (d, J = 14.0 Hz, 1H), 4.00 (q, J = 7.3 Hz, 2H), 3.90 (d, J = 11.0 Hz, 1H), 3.84 – 3.70 (m, 5H), 3.63 (d, J = 12.1 Hz, 2H), 2.94 (t, J = 7.2 Hz, 2H), 2.48 (d, J = 3.2 Hz, 5H), 2.31 – 2.09 (m, 12H), 1.66 – 1.57 (m, 6H), 1.37 (s, 6H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₇₁H₈₈N₉O₁₁S ⁺ [M + H]⁺, 1274.6319; found, 1274.6822. Example 84 Synthesis of NS106-077

yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N19-(6-(3- ((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-4,7,10,13,16- pentaoxanonadecanediamide. NS106-077 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-21-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)- 22,22-dimethyl-19-oxo-4,7,10,13,16-pentaoxa-20-azatricosanoic acid. (white solid, 9.6 mg, 37%) ¹H NMR (800 MHz, Methanol-d4) δ 8.92 (s, 1H), 8.72 (s, 1H), 7.48 – 7.31 (m, 12H), 7.21 – 7.09 (m, 4H), 6.86 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.65 (s, 1H), 4.57 – 4.48 (m, 3H), 4.44 (t, J = 11.7 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H), 3.88 (d, J = 10.9 Hz, 1H), 3.83-3.78 (m, 1H), 3.75 (d, J = 11.3 Hz, 1H), 3.70 (t, J = 6.3 Hz, 4H), 3.62 – 3.57 (m, 16H), 3.23 (t, J = 6.7 Hz, 2H), 2.58-2.54 (m, 2H), 2.47 (s, 3H), 2.41 (dt, J = 21.2, 6.4 Hz, 4H), 2.21 – 2.10 (m, 8H), 1.65 – 1.58 (m, 6H), 1.03 (s, 9H).HRMS (ESI) m/z: calcd for C₇₃H₉₂N₉O₁₁S ⁺ [M + H]⁺, 1302.6632; found, 1302.8180. Example 85 Synthesis of NS113-028

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((2-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-2-oxoethyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-028 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and ((S)-3-((2S,4R)- 1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanoyl)glycine. (white solid, 10.3 mg, 44%) ¹H NMR (600 MHz, Methanol-d4) δ 8.88 (s, 1H), 8.85 (d, J = 8.1 Hz, 1H), 8.72 (s, 1H), 7.47 (d, J = 5.7 Hz, 2H), 7.45 – 7.42 (m, 2H), 7.40 – 7.37 (m, 3H), 7.35 – 7.30 (m, 4H), 7.19 – 7.16 (m, 1H), 7.13 (dt, J = 7.0, 1.4 Hz, 2H), 7.09 (t, J = 7.7 Hz, 1H), 6.86 (t, J = 1.8 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.46 – 5.44 (m, 2H), 5.40 (q, J = 7.7, 7.3 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.60 – 4.56 (m, 1H), 4.44 (d, J = 9.8 Hz, 2H), 3.87 – 3.82 (m, 2H), 3.80 – 3.75 (m, 3H), 3.21 (dt, J = 9.8, 6.0 Hz, 2H), 2.92 – 2.84 (m, 2H), 2.46 (d, J = 1.7 Hz, 3H), 2.37 (t, J = 6.9 Hz, 2H), 2.20 – 2.10 (m, 7H), 2.02-1.96 (m, 1H), 1.63 – 1.53 (m, 6H), 1.35 – 1.28 (m, 4H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₆₇H₇₆FN₁₀O₇S⁺ [M + H]⁺, 1183.5598; found, 1183.5529. Example 86 Synthesis of NS113-029

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((3-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-3-oxopropyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-029 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)propanoic acid. (white solid, 10.8 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 9.45 (s, 1H), 8.89 (d, J = 7.7 Hz, 1H), 8.70 (d, J = 7.4 Hz, 1H), 7.51– 7.37 (m, 7H), 7.33 (t, J = 7.7 Hz, 2H), 7.27 (d, J = 6.6 Hz, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 7.1 Hz, 2H), 7.11 (t, J = 7.8 Hz, 1H), 6.92 (s, 1H), 6.82 (d, J = 7.7 Hz, 1H), 5.59 (s, 1H), 5.37-5.31 (m, 2H), 4.76 – 4.72 (m, 1H), 4.58 (d, J = 7.8 Hz, 2H), 4.43 (s, 1H), 3.84 – 3.82 (m, 1H), 3.75-3.72 (m, 2H), 3.15 (t, J = 6.6 Hz, 2H), 3.12 – 3.05 (m, 2H), 3.04 – 3.01 (m, 1H), 2.99 – 2.93 (m, 1H), 2.86-2.83 (m, 2H), 2.79-2.71 (m, 2H), 2.45 (s, 3H), 2.36 (t, J = 6.6 Hz, 2H), 2.21 – 2.15 (m, 2H), 2.05 – 1.92 (m, 4H), 1.68 – 1.55 (m, 6H), 1.38– 1.26 (m, 8H), 1.05 (s, 9H).. HRMS (ESI) m/z: calcd for C₆₈H₇₈FN₁₀O₇S⁺ [M + H]⁺, 1197.5754; found, 1197.5596. Example 87 Synthesis of NS113-030

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((4-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-4-oxobutyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-030 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 4-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)butanoic acid. (white solid, 11.2 mg, 46%) 1H NMR (600 MHz, Methanol-d4) δ 9.46 (s, 1H), 8.88 (d, J = 7.7 Hz, 1H), 8.71 (d, J = 7.4 Hz, 1H), 7.50 – 7.37 (m, 7H), 7.34 (t, J = 7.7 Hz, 2H), 7.26 (d, J = 6.6 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.16 (d, J = 7.1 Hz, 2H), 7.11 (t, J = 7.8 Hz, 1H), 6.90 (s, 1H), 6.81 (d, J = 7.7 Hz, 1H), 5.58 (s, 1H), 5.37-5.32 (m, 2H), 4.75 – 4.72 (m, 1H), 4.57 (d, J = 7.8 Hz, 2H), 4.44 (s, 1H), 3.85 – 3.82 (m, 1H), 3.76 (dd, J = 11.1, 3.8 Hz, 2H), 3.16 (t, J = 6.6 Hz, 2H), 3.11 – 3.05 (m, 2H), 3.03 – 3.00 (m, 1H), 2.98 – 2.93 (m, 1H), 2.84 (dd, J = 14.2, 6.3 Hz, 2H), 2.78-2.71 (m, 2H), 2.46 (s, 3H), 2.37 (t, J = 6.6 Hz, 2H), 2.22 – 2.15 (m, 4H), 2.03 – 1.92 (m, 4H), 1.67 – 1.53 (m, 6H), 1.37 – 1.25 (m, 8H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₆₉H₈₀FN₁₀O₇S⁺ [M + H]⁺, 1211.5911; found, 1211.4668. Example 88 Synthesis of NS113-031

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-5-oxopentyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-031 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 5-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)pentanoic acid. (white solid, 10.9 mg, 44%) 1H NMR (600 MHz, Methanol-d4) δ 9.44 (s, 1H), 8.91 (s, 1H), 8.72 (s, 1H), 7.50 – 7.41 (m, 6H), 7.40-7.36 (m, 4H), 7.33 (dt, J = 6.6, 2.1 Hz, 2H), 7.32 – 7.30 (m, 1H), 7.20 – 7.17 (m, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.9 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.3, 6.0 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.58 (dd, J = 9.3, 7.6 Hz, 1H), 4.47 – 4.42 (m, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.76 (dd, J = 11.0, 3.9 Hz, 2H), 3.17 (t, J = 6.7 Hz, 2H), 3.12 (d, J = 6.8 Hz, 1H), 3.06 (d, J = 6.7 Hz, 1H), 2.86 – 2.82 (m, 1H), 2.76 – 2.72 (m, 1H), 2.47 (s, 3H), 2.38 (t, J = 6.7 Hz, 2H), 2.20 – 2.15 (m, 4H), 2.11 (t, J = 7.3 Hz, 3H), 1.99-1.92 (m, 1H), 1.64 – 1.55 (m, 6H), 1.49 – 1.45 (m, 2H), 1.40 – 1.28 (m, 8H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₇S⁺ [M + H]⁺, 1225.6067; found, 1225.6250. Example 89 Synthesis of NS113-032

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((6-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-6-oxohexyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-032 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)hexanoic acid. (white solid, 11.3 mg, 46%) 1H NMR (600 MHz, Methanol-d₄) δ 9.44 (s, 1H), 8.89 (s, 1H), 8.72 (s, 1H), 7.49 – 7.42 (m, 6H), 7.39 (dd, J = 5.2, 2.0 Hz, 2H), 7.35 – 7.30 (m, 2H), 7.28 – 7.25 (m, 1H), 7.20 – 7.13 (m, 3H), 7.11 (dd, J = 7.8, 2.1 Hz, 1H), 6.89 (s, 1H), 6.81 (d, J = 7.6 Hz, 1H), 5.45 (s, 1H), 5.34 – 5.27 (m, 2H), 4.75 – 4.72 (m, 1H), 4.57 (d, J = 8.6 Hz, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.79 – 3.75 (m, 2H), 3.19 (d, J = 6.3 Hz, 1H), 3.11 – 3.02 (m, 3H), 2.86 – 2.82 (m, 1H), 2.74 (dd, J = 9.9, 4.1 Hz, 1H), 2.46 (s, 3H), 2.39 (td, J = 6.7, 2.9 Hz, 2H), 2.19 (t, J = 10.6 Hz, 5H), 2.10 (t, J = 7.5 Hz, 2H), 1.99-1.92 (m, 2H), 1.85 (t, J = 7.4 Hz, 1H), 1.64 – 1.52 (m, 6H), 1.37 – 1.28 (m, 8H), 1.23-1.18 (m, 2H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₁H₈₄FN₁₀O₇S⁺ [M + H]⁺, 1239.6224; found, 1239.4838. Example 90 Synthesis of NS113-033

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((7-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-7-oxoheptyl)amino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-033 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 7-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)heptanoic acid. (white solid, 11.1 mg, 44%) 1H NMR (600 MHz, Methanol-d4) δ 8.91 (s, 1H), 8.72 (s, 1H), 7.48 – 7.42 (m, 4H), 7.41 – 7.36 (m, 4H), 7.35 – 7.30 (m, 4H), 7.19 – 7.17 (m, 1H), 7.14 (dt, J = 7.0, 1.3 Hz, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.9 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.5, 5.9 Hz, 1H), 4.76 – 4.72 (m, 1H), 4.58 (dd, J = 9.2, 7.5 Hz, 1H), 4.44 (s, 2H), 3.83 (d, J = 11.2 Hz, 1H), 3.76 (dd, J = 11.0, 4.0 Hz, 2H), 3.19 (t, J = 6.7 Hz, 2H), 3.11 – 3.06 (m, 1H), 3.02 (q, J = 6.7 Hz, 1H), 2.86-2.81 (m, 1H), 2.75-2.71 (m, 1H), 2.47 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.21 – 2.15 (m, 5H), 2.14 – 2.08 (m, 4H), 1.98-1.93 (m, 1H), 1.65 – 1.56 (m, 6H), 1.52 (t, J = 7.5 Hz, 2H), 1.37 – 1.28 (m, 6H), 1.26 – 1.21 (m, 2H), 1.17 (q, J = 7.3 Hz, 2H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₂H₈₆FN₁₀O₇S⁺ [M + H]⁺, 1253.6380; found, 1253.7073. Example 91 Synthesis of NS113-034

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((8-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-8-oxooctyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-034 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 8-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)octanoic acid. (white solid, 11.7 mg, 46%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.91 (s, 1H), 8.72 (s, 1H), 7.48 – 7.42 (m, 4H), 7.40-7.36 (m, 4H), 7.34 – 7.30 (m, 4H), 7.18 (dd, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.9 Hz, 1H), 6.80 – 6.77 (m, 1H), 5.45 (s, 2H), 5.31 (dd, J = 8.5, 5.9 Hz, 1H), 4.76-4.73 (m, 1H), 4.58 (dd, J = 9.3, 7.5 Hz, 1H), 4.44 (dd, J = 4.2, 2.4 Hz, 2H), 3.84 – 3.81 (m, 1H), 3.78-3.73 (m, 2H), 3.20 (t, J = 6.7 Hz, 2H), 3.10 – 3.06 (m, 1H), 3.04 – 3.00 (m, 1H), 2.86-2.81 (m, 1H), 2.75-2.71 (m, 1H), 2.47 (d, J = 2.2 Hz, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.21 – 2.15 (m, 5H), 2.14 – 2.08 (m, 4H), 1.96 (td, J = 9.1, 4.7 Hz, 1H), 1.65 – 1.56 (m, 6H), 1.53 (t, J = 7.3 Hz, 2H), 1.35-1.31 (m, 6H), 1.25- 1.19 (m, 4H), 1.13 (d, J = 7.5 Hz, 2H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₃H₈₈FN₁₀O₇S⁺ [M + H]⁺, 1267.6537; found, 1267.6721. Example 92 Synthesis of NS113-083

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-3-((2-(3-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-3-oxopropoxy)ethyl)amino)-1-(3-(4-methylthiazol-5-yl)phenyl)-3- oxopropyl)pyrrolidine-2-carboxamide. NS113-083 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-((S)-3- ((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)-3-(4-(4-methylthiazol-5- yl)phenyl)propanamido)ethoxy)propanoic acid. (white solid, 10.8 mg, 43%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.86 (d, J = 1.5 Hz, 1H), 8.71 (s, 1H), 8.69 (d, J = 7.8 Hz, 1H), 7.49 – 7.41 (m, 4H), 7.38 (dt, J = 4.9, 2.5 Hz, 4H), 7.34 – 7.30 (m, 3H), 7.17 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.09 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.44 (s, 2H), 5.32 (d, J = 7.1 Hz, 1H), 4.73 (d, J = 9.4 Hz, 1H), 4.58 (t, J = 8.5 Hz, 1H), 4.43 (d, J = 4.2 Hz, 2H), 3.82 (d, J = 11.1 Hz, 1H), 3.75 (dt, J = 11.1, 4.1 Hz, 2H), 3.65 – 3.60 (m, 2H), 3.43 – 3.35 (m, 4H), 3.28 – 3.20 (m, 4H), 2.83 (dd, J = 14.1, 6.4 Hz, 1H), 2.74 (dd, J = 14.2, 8.0 Hz, 1H), 2.45 (s, 3H), 2.38 (d, J = 6.3 Hz, 2H), 2.19-2.14 (m, 5H), 2.11 (d, J = 12.2 Hz, 2H), 1.98 – 1.94 (m, 1H), 1.65 – 1.54 (m, 6H), 1.37 – 1.25 (m, 4H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₈S+ [M + H]⁺, 1241.6016; found, 1241.9353. Example 93 Synthesis of NS113-084

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-20-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-1-(4-(4-methylthiazol- 5-yl)phenyl)-3,13-dioxo-7,10-dioxa-4,14-diazaicos-19-yn-1-yl)pyrrolidine-2- carboxamide. NS113-084 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (S)-1-((2S,4R)-1-((S)-2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidin-2- yl)-3-(4-(4-methylthiazol-5-yl)phenyl)-1,5-dioxo-9,12-dioxa-2,6-diazapentadecan-15- oic acid. (white solid, 11.5 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.88 (s, 1H), 8.72 (s, 1H), 8.69 (d, J = 7.7 Hz, 1H), 7.44 (q, J = 9.3, 8.7 Hz, 5H), 7.40 – 7.37 (m, 3H), 7.34 – 7.30 (m, 3H), 7.17 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 7.3 Hz, 2H), 7.11 (d, J = 7.8 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 5.45 (s, 2H), 5.32 (d, J = 7.1 Hz, 1H), 4.73 (d, J = 9.4 Hz, 1H), 4.59 (d, J = 8.6 Hz, 1H), 4.43 (s, 2H), 3.83 (s, 1H), 3.75 (dd, J = 10.7, 4.0 Hz, 2H), 3.69 (d, J = 6.0 Hz, 2H), 3.53 (t, J = 4.6 Hz, 2H), 3.51 – 3.48 (m, 2H), 3.43 – 3.39 (m, 1H), 3.38 – 3.34 (m, 1H), 3.27 (d, J = 5.5 Hz, 2H), 3.20 – 3.17 (m, 2H), 2.86 (d, J = 7.9 Hz, 1H), 2.77 – 2.74 (m, 1H), 2.46 (s, 3H), 2.41 (d, J = 6.1 Hz, 2H), 2.36 (s, 2H), 2.19-2.15 (m, 5H), 2.11 (d, J = 12.1 Hz, 2H), 1.95 (s, 1H), 1.63 – 1.53 (m, 6H), 1.33-1.27 (m, 4H), 1.05 (s, 9H). HRMS (ESI) m/z: calcd for C₇₂H₈₆FN₁₀O₉S⁺ [M + H]⁺, 1285.6278; found, 1285.6726. Example 94 Synthesis of NS113-085

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-23-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-1-(3-(4-methylthiazol- 5-yl)phenyl)-3,16-dioxo-7,10,13-trioxa-4,17-diazatricos-22-yn-1-yl)pyrrolidine-2- carboxamide. NS113-085 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (3S)-1-((2S,4R)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidin-2- yl)-3-(4-(4-methylthiazol-5-yl)phenyl)-1,5-dioxo-9,12,15-trioxa-2,6-diazaoctadecan- 18-oic acid. (white solid, 11.1 mg, 42%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.72 (s, 1H), 7.48 – 7.43 (m, 4H), 7.41 – 7.37 (m, 4H), 7.34 – 7.30 (m, 4H), 7.18 (dt, J = 7.7, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.78 (dt, J = 7.8, 1.5 Hz, 1H), 5.45 (s, 2H), 5.33 (dd, J = 8.1, 6.1 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.58 (dd, J = 9.3, 7.5 Hz, 1H), 4.44 (t, J = 3.3 Hz, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.78 – 3.74 (m, 2H), 3.70 (t, J = 6.1 Hz, 2H), 3.55 (d, J = 13.6 Hz, 6H), 3.50 – 3.47 (m, 2H), 3.43 – 3.40 (m, 1H), 3.38 – 3.35 (m, 1H), 3.30 – 3.24 (m, 2H), 3.21 (t, J = 6.7 Hz, 2H), 2.84 (dd, J = 14.2, 6.2 Hz, 1H), 2.76 (dd, J = 14.2, 8.2 Hz, 1H), 2.47 (d, J = 2.0 Hz, 3H), 2.41 (t, J = 6.1 Hz, 2H), 2.38 (t, J = 6.8 Hz, 2H), 2.21 – 2.15 (m, 5H), 2.14-2.10 (m, 2H), 1.96 (td, J = 9.1, 4.7 Hz, 1H), 1.65 – 1.56 (m, 6H), 1.37 – 1.26 (m, 4H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C₇₄H₉₀FN₁₀O₁₀S⁺ [M + H]⁺, 1329.6541; found, 1329.6813. Example 95 Synthesis of NS113-086

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-26-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-1-(4-(4- methylthiazol-5-yl)phenyl)-3,19-dioxo-7,10,13,16-tetraoxa-4,20-diazahexacos-25- yn-1-yl)pyrrolidine-2-carboxamide. NS113-086 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (3S)-1-((2S,4R)- 1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidin-2-yl)-3-(4-(4-methylthiazol-5-yl)phenyl)-1,5-dioxo-9,12,15,18- tetraoxa-2,6-diazahenicosan-21-oic acid. (white solid, 12.2 mg, 44%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.72 (s, 1H), 7.48 – 7.43 (m, 4H), 7.40 – 7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.20 – 7.17 (m, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.80 – 6.77 (m, 1H), 5.45 (s, 2H), 5.33 (dd, J = 8.1, 6.1 Hz, 1H), 4.75 – 4.71 (m, 1H), 4.58 (dd, J = 9.2, 7.5 Hz, 1H), 4.46 – 4.42 (m, 2H), 3.83 (d, J = 11.1 Hz, 1H), 3.79 – 3.74 (m, 2H), 3.70 (t, J = 6.1 Hz, 2H), 3.60 – 3.53 (m, 10H), 3.51 – 3.48 (m, 2H), 3.46 – 3.41 (m, 1H), 3.39 – 3.36 (m, 1H), 3.30 – 3.25 (m, 2H), 3.22 (t, J = 6.7 Hz, 2H), 2.84 (dd, J = 14.2, 6.1 Hz, 1H), 2.76 (dd, J = 14.2, 8.1 Hz, 1H), 2.48 (s, 3H), 2.40 (dt, J = 17.9, 6.4 Hz, 4H), 2.22 – 2.15 (m, 5H), 2.12 (dd, J = 12.4, 3.2 Hz, 2H), 1.96 (td, J = 9.1, 4.7 Hz, 1H), 1.65 – 1.55 (m, 6H), 1.38 – 1.27 (m, 4H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C₇₆H₉₄FN₁₀O₁₁S⁺ [M + H]⁺, 1373.6803; found, 1373.7703. Example 96 Synthesis of NS113-087

(2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxy-N-((S)-29-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-1-(3-(4-methylthiazol- 5-yl)phenyl)-3,22-dioxo-7,10,13,16,19-pentaoxa-4,23-diazanonacos-28-yn-1- yl)pyrrolidine-2-carboxamide. NS113-087 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (3S)-1-((2S,4R)-1-(2-(1- fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidin-2- yl)-3-(4-(4-methylthiazol-5-yl)phenyl)-1,5-dioxo-9,12,15,18,21-pentaoxa-2,6- diazatetracosan-24-oic acid. (white solid, 11.9 mg, 42%) ¹H NMR (600 MHz, Methanol-d4) δ 8.96 (s, 1H), 8.72 (s, 1H), 7.49 – 7.43 (m, 4H), 7.41-7.37 (m, 4H), 7.35 – 7.30 (m, 4H), 7.18 (dt, J = 7.7, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.79 (dt, J = 8.0, 1.4 Hz, 1H), 5.45 (s, 2H), 5.33 (dd, J = 8.1, 6.1 Hz, 1H), 4.74 (dd, J = 9.4, 1.2 Hz, 1H), 4.58 (dd, J = 9.2, 7.5 Hz, 1H), 4.44 (t, J = 3.4 Hz, 2H), 3.84 – 3.81 (m, 1H), 3.78 – 3.74 (m, 2H), 3.70 (t, J = 6.1 Hz, 2H), 3.59 – 3.54 (m, 14H), 3.53 – 3.49 (m, 2H), 3.46 – 3.42 (m, 1H), 3.40 – 3.36 (m, 1H), 3.30 – 3.25 (m, 2H), 3.22 (t, J = 6.7 Hz, 2H), 2.84 (dd, J = 14.2, 6.1 Hz, 1H), 2.76 (dd, J = 14.1, 8.1 Hz, 1H), 2.48 (s, 3H), 2.40 (dt, J = 17.0, 6.4 Hz, 4H), 2.23 – 2.15 (m, 5H), 2.14 – 2.08 (m, 2H), 1.96 (td, J = 9.1, 4.7 Hz, 1H), 1.66 – 1.57 (m, 6H), 1.38 – 1.26 (m, 4H), 1.05 (s, 9H).HRMS (ESI) m/z: calcd for C₇₈H₉₈FN₁₀O₁₂S⁺ [M + H]⁺, 1417.7065; found, 1417.7214. Example 97 Synthesis of NS113-039

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((2-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-2-oxoethyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-039 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and (2-(2-(((2S,4R)- 1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetyl)glycine. (white solid, 10.7 mg, 45%) ¹H NMR (600 MHz, Methanol- d₄) δ 8.97 (s, 1H), 8.72 (s, 1H), 7.48 (d, J = 7.8 Hz, 2H), 7.40 – 7.37 (m, 4H), 7.35 – 7.33 (m, 2H), 7.32 (d, J = 1.3 Hz, 1H), 7.18 (dt, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.08 (m, 2H), 7.01 (d, J = 1.6 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.77 (dt, J = 8.0, 1.4 Hz, 1H), 5.44 (s, 2H), 4.75 – 4.71 (m, 2H), 4.69 (d, J = 14.7 Hz, 1H), 4.63 (d, J = 14.7 Hz, 1H), 4.55 (dd, J = 9.3, 7.6 Hz, 1H), 4.48 – 4.43 (m, 2H), 4.36 (d, J = 14.9 Hz, 1H), 3.99 (d, J = 16.5 Hz, 1H), 3.91 (d, J = 16.5 Hz, 1H), 3.83 (d, J = 11.0 Hz, 1H), 3.79 – 3.74 (m, 2H), 3.24 (td, J = 6.8, 2.7 Hz, 2H), 2.49 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.21 – 2.15 (m, 5H), 2.14 – 2.10 (m, 2H), 2.10 – 2.06 (m, 1H), 1.66 – 1.57 (m, 6H), 1.36 – 1.27 (m, 4H), 0.96 (s, 9H).HRMS (ESI) m/z: calcd for C₆₇H₇₆FN₁₀O₈S ⁺ [M + H]⁺, 1199.5547; found, 1199.6605. Example 98 Synthesis of NS113-040

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((3-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-3-oxopropyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-040 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)propanoic acid. (white solid, 10.9 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.93 (s, 1H), 8.72 (s, 1H), 7.48 (d, J = 7.8 Hz, 2H), 7.40 – 7.36 (m, 4H), 7.34 – 7.32 (m, 2H), 7.30 (d, J = 7.5 Hz, 1H), 7.15 (dt, J = 7.7, 1.3 Hz, 1H), 7.13 (dt, J = 7.1, 1.3 Hz, 2H), 7.08 (ddd, J = 7.7, 4.7, 3.1 Hz, 2H), 6.95 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.76 (dt, J = 7.8, 1.5 Hz, 1H), 5.43 (s, 2H), 4.74 – 4.71 (m, 1H), 4.58 (q, J = 8.4, 8.0 Hz, 4H), 4.49 – 4.43 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.81 – 3.73 (m, 2H), 3.60 – 3.52 (m, 2H), 3.20 (t, J = 6.7 Hz, 2H), 2.48 (t, J = 6.8 Hz, 2H), 2.46 (s, 3H), 2.35 (t, J = 6.8 Hz, 2H), 2.21 – 2.14 (m, 5H), 2.14 – 2.10 (m, 2H), 2.08 (td, J = 9.0, 4.6 Hz, 1H), 1.64 – 1.54 (m, 6H), 1.37 – 1.27 (m, 4H), 0.99 (s, 9H).HRMS (ESI) m/z: calcd for C₆₈H₇₈FN₁₀O₈S ⁺ [M + H]⁺, 1213.5703; found, 1213.4180. Example 99 Synthesis of NS113-041

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((4-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-4-oxobutyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-041 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 4-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)butanoic acid. (white solid, 10.1 mg, 41%) ¹H NMR (600 MHz, Methanol-d4) δ 8.91 (s, 1H), 8.72 (s, 1H), 7.49 – 7.46 (m, 2H), 7.41 – 7.37 (m, 4H), 7.34 (dt, J = 4.8, 2.6 Hz, 2H), 7.31 (d, J = 7.7 Hz, 1H), 7.18 (dt, J = 7.7, 1.4 Hz, 1H), 7.13 (dt, J = 6.9, 1.3 Hz, 2H), 7.11 – 7.07 (m, 2H), 6.96 (d, J = 1.6 Hz, 1H), 6.86 (t, J = 1.8 Hz, 1H), 6.78 – 6.76 (m, 1H), 5.44 (s, 2H), 4.74 – 4.71 (m, 1H), 4.63 – 4.54 (m, 4H), 4.49 – 4.41 (m, 3H), 3.85 – 3.75 (m, 3H), 3.33 (d, J = 6.9 Hz, 2H), 3.19 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.38 (t, J = 6.8 Hz, 2H), 2.24 – 2.17 (m, 7H), 2.16 – 2.12 (m, 2H), 2.09 – 2.05 (m, 1H), 1.88 – 1.84 (m, 2H), 1.65 – 1.56 (m, 6H), 1.36 – 1.26 (m, 4H), 1.00 (s, 9H).HRMS (ESI) m/z: calcd for C₆₉H₈₀FN₁₀O₈S ⁺ [M + H]⁺, 1227.5860; found, 1227.5762. Example 100 Synthesis of NS113-042

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-5-oxopentyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-042 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 5-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)pentanoic acid. (white solid, 11.2 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.96 (s, 1H), 8.71 (s, 1H), 7.48 (d, J = 7.7 Hz, 2H), 7.40 – 7.37 (m, 4H), 7.34 – 7.30 (m, 3H), 7.19 – 7.16 (m, 1H), 7.15 – 7.12 (m, 2H), 7.10 – 7.07 (m, 2H), 6.95 (d, J = 1.7 Hz, 1H), 6.85 (t, J = 1.8 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.74 – 4.71 (m, 1H), 4.60 – 4.55 (m, 4H), 4.50 – 4.42 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.81 – 3.75 (m, 2H), 3.30 – 3.27 (m, 2H), 3.20 (t, J = 6.7 Hz, 2H), 2.48 (s, 3H), 2.39 (t, J = 6.8 Hz, 2H), 2.23 – 2.15 (m, 7H), 2.15 – 2.10 (m, 2H), 2.07 (td, J = 9.1, 4.6 Hz, 1H), 1.65 – 1.56 (m, 10H), 1.36 – 1.27 (m, 4H), 1.00 (s, 9H).HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₈S ⁺ [M + H]⁺, 1241.6016; found, 1241.7852. Example 101 Synthesis of NS113-043

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((6-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-6-oxohexyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-043 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 6-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)hexanoic acid. (white solid, 10.9 mg, 43%) ¹H NMR (600 MHz, Methanol-d4) δ 8.92 (s, 1H), 8.71 (s, 1H), 7.48 (d, J = 7.7 Hz, 2H), 7.41 – 7.37 (m, 4H), 7.35 – 7.32 (m, 2H), 7.32 – 7.30 (m, 1H), 7.18 (dt, J = 7.9, 1.4 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.08 (m, 2H), 6.96 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 1.7 Hz, 1H), 6.79 – 6.76 (m, 1H), 5.44 (s, 2H), 4.74 – 4.71 (m, 1H), 4.62 – 4.55 (m, 4H), 4.49 – 4.41 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.79-3.75 (m, 2H), 3.27 (dd, J = 7.1, 3.8 Hz, 2H), 3.20 (t, J = 6.8 Hz, 2H), 2.48 (s, 3H), 2.38 (t, J = 6.8 Hz, 2H), 2.22 – 2.04 (m, 10H), 1.67 – 1.52 (m, 10H), 1.36 – 1.25 (m, 6H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₁H₈₄FN₁₀O₈S + [M + H]⁺, 1255.6173; found, 1255.6741. Example 102 Synthesis of NS113-088

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-(2-((2-(3-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6- diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn- 1-yl)amino)-3-oxopropoxy)ethyl)amino)-2-oxoethoxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-088 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)ethoxy)propanoic acid. (white solid, 12.3 mg, 49%) ¹H NMR (600 MHz, Methanol-d4) δ 8.89 (s, 1H), 8.71 (s, 1H), 7.50 – 7.46 (m, 2H), 7.41 – 7.36 (m, 4H), 7.33 (dd, J = 7.2, 2.4 Hz, 2H), 7.31 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 7.7 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.10 – 7.07 (m, 2H), 6.96 (d, J = 1.6 Hz, 1H), 6.85 (s, 1H), 6.76 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.73 (d, J = 9.3 Hz, 1H), 4.61 – 4.54 (m, 4H), 4.50 – 4.42 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.80 – 3.74 (m, 2H), 3.67 (td, J = 6.2, 1.7 Hz, 2H), 3.56 (t, J = 5.6 Hz, 2H), 3.46 (t, J = 5.7 Hz, 2H), 3.18 (t, J = 6.8 Hz, 2H), 2.47 (s, 3H), 2.38-2.34 (m, 4H), 2.21 – 2.04 (m, 8H), 1.63 – 1.52 (m, 6H), 1.37 – 1.27 (m, 4H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₀H₈₂FN₁₀O₉S ⁺ [M + H]⁺, 1257.5965; found, 1257.5782. Example 103 Synthesis of NS113-089

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-((19-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-2,12-dioxo-6,9- dioxa-3,13-diazanonadec-18-yn-1-yl)oxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-089 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(2-(2-(2-(2- (((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5- yl)phenoxy)acetamido)ethoxy)ethoxy)propanoic acid. (white solid, 11.9 mg, 46%) ¹H NMR (600 MHz, Methanol-d4) δ 8.93 (s, 1H), 8.71 (s, 1H), 7.49 (t, J = 6.9 Hz, 2H), 7.41 – 7.37 (m, 4H), 7.35 – 7.32 (m, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.17 (dt, J = 7.7, 1.4 Hz, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.07 (m, 2H), 6.97 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.77 (dt, J = 7.8, 1.5 Hz, 1H), 5.44 (s, 2H), 4.75 – 4.72 (m, 1H), 4.64 – 4.53 (m, 4H), 4.51 – 4.41 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.80 – 3.74 (m, 2H), 3.69 (t, J = 6.1 Hz, 2H), 3.58 – 3.52 (m, 6H), 3.45 (t, J = 5.7 Hz, 2H), 3.20 (t, J = 6.7 Hz, 2H), 2.48 (s, 3H), 2.39 (dt, J = 20.0, 6.4 Hz, 4H), 2.22 – 2.05 (m, 8H), 1.64 – 1.53 (m, 6H), 1.37 – 1.24 (m, 4H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₂H₈₆FN₁₀O₁₀S + [M + H]⁺, 1301.6228; found, 1301.7304. Example 104 Synthesis of NS113-090

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-((22-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-2,15-dioxo-6,9,12- trioxa-3,16-diazadocos-21-yn-1-yl)oxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide (113090). NS113-090 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 1- (2-(((2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5-yl)phenoxy)-2- oxo-6,9,12-trioxa-3-azapentadecan-15-oic acid. (white solid, 12.4 mg, 46%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.89 (s, 1H), 8.72 (s, 1H), 7.49 (d, J = 7.7 Hz, 2H), 7.41 – 7.37 (m, 4H), 7.35 – 7.32 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.19 – 7.16 (m, 1H), 7.15 – 7.12 (m, 2H), 7.11 – 7.07 (m, 2H), 6.96 (d, J = 1.6 Hz, 1H), 6.86 (d, J = 2.0 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.73 (d, J = 9.1 Hz, 1H), 4.63 – 4.53 (m, 4H), 4.51 – 4.42 (m, 3H), 3.84 (d, J = 11.1 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.69 (t, J = 6.1 Hz, 2H), 3.61 – 3.51 (m, 10H), 3.47 (q, J = 5.6 Hz, 2H), 3.21 (t, J = 6.7 Hz, 2H), 2.47 (s, 3H), 2.41-2.36 (m, 4H), 2.23 – 2.08 (m, 8H), 1.66 – 1.55 (m, 6H), 1.36 – 1.27 (m, 4H), 1.01 (s, 9H). HRMS (ESI) m/z: calcd for C₇₄H₉₀FN₁₀O₁₁S ⁺ [M + H]⁺, 1345.6490; found, 1345.8031. Example 105 Synthesis of NS113-091

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-((25-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-2,18-dioxo- 5 6,9,12,15-tetraoxa-3,19-diazapentacos-24-yn-1-yl)oxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide. NS113-091 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 1-(2-(((2S,4R)- 1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5-yl)phenoxy)-2-oxo- 10 6,9,12,15-tetraoxa-3-azaoctadecan-18-oic acid. (white solid, 12.6 mg, 45%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.96 (s, 1H), 8.71 (s, 1H), 7.49 (dd, J = 10.9, 7.1 Hz, 2H), 7.41-7.36 (m, 4H), 7.34 – 7.32 (m, 2H), 7.32 – 7.30 (m, 1H), 7.19 – 7.17 (m, 1H), 7.15 – 7.12 (m, 2H), 7.12 – 7.08 (m, 2H), 6.97 (d, J = 1.6 Hz, 1H), 6.85 (t, J = 1.8 Hz, 1H), 6.79 – 6.77 (m, 1H), 5.44 (s, 2H), 4.75 – 4.72 (m, 1H), 4.64 – 4.53 (m, 4H), 4.51 – 4.42 15 (m, 3H), 3.86 – 3.82 (m, 1H), 3.81 – 3.73 (m, 2H), 3.69 (t, J = 6.1 Hz, 2H), 3.61 – 3.54 (m, 14H), 3.47 (t, J = 5.7 Hz, 2H), 3.22 (t, J = 6.7 Hz, 2H), 2.49 (s, 3H), 2.42-2.38 (m, 4H), 2.22 – 2.07 (m, 8H), 1.65 – 1.56 (m, 6H), 1.36 – 1.25 (m, 4H), 1.01 (s, 9H).HRMS (ESI) m/z: calcd for C₇₆H₉₄FN₁₀O₁₂S ⁺ [M + H]⁺, 1389.6752; found, 1389.7125. 20 Example 106 Synthesis of NS113-092

(2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-(2-((28-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)-2,21-dioxo- 6,9,12,15,18-pentaoxa-3,22-diazaoctacos-27-yn-1-yl)oxy)-4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide). NS113-092 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 1-(2-(((2S,4R)- 1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamido)methyl)-5-(4-methylthiazol-5-yl)phenoxy)-2-oxo- 6,9,12,15,18-pentaoxa-3-azahenicosan-21-oic acid. (white solid, 11.7 mg, 41%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.72 (s, 1H), 7.52 – 7.47 (m, 2H), 7.41- 7.36 (m, 4H), 7.38-7.34 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.18 (dt, J = 7.7, 1.4 Hz, 1H), 7.16 – 7.13 (m, 2H), 7.12 – 7.08 (m, 2H), 6.98 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.80 – 6.77 (m, 1H), 5.45 (s, 2H), 4.75 – 4.72 (m, 1H), 4.64 – 4.54 (m, 4H), 4.51 – 4.42 (m, 3H), 3.84 (d, J = 11.4 Hz, 1H), 3.82 – 3.74 (m, 2H), 3.69 (t, J = 6.1 Hz, 2H), 3.63 – 3.53 (m, 18H), 3.47 (t, J = 5.5 Hz, 2H), 3.22 (t, J = 6.7 Hz, 2H), 2.49 (s, 3H), 2.43-2.37 (m, 4H), 2.24 – 2.08 (m, 8H), 1.65 – 1.55 (m, 6H), 1.37 – 1.25 (m, 4H), 1.01 (s, 9H). HRMS (ESI) m/z: calcd for C₇₈H₉₈FN₁₀O₁₃S ⁺ [M + H]⁺, 1433.7014; found, 1433.8123. Example 107 Synthesis of NS113-075

(2S,4R)-4-hydroxy-1-((S)-2-(4-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent- 4-yn-1-yl)piperazin-1-yl)-4-oxobutanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-075 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 4- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-oxobutanoic acid. (white solid, 10.9 mg, 48%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.72 (d, J = 2.3 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.43 – 7.36 (m, 6H), 7.34 – 7.27 (m, 6H), 7.17 – 7.14 (m, 2H), 7.12 (s, 1H), 6.98 (s, 1H), 6.92 (d, J = 4.7 Hz, 1H), 5.56 (s, 2H), 4.73 (d, J = 17.1 Hz, 1H), 4.63 (s, 1H), 4.58 – 4.51 (m, 2H), 4.49 – 4.42 (m, 2H), 4.36 (d, J = 15.5 Hz, 1H), 4.32 – 4.25 (m, 1H), 4.07 – 4.00 (m, 2H), 3.96 – 3.86 (m, 2H), 3.78-3.73 (m, 5H), 3.63 (d, J 10 = 12.5 Hz, 2H), 2.98 – 2.92 (m, 2H), 2.84 – 2.71 (m, 2H), 2.70 – 2.66 (m, 1H), 2.60 (s, 1H), 2.48 (s, 3H), 2.28 (dt, J = 10.9, 7.0 Hz, 2H), 2.21 – 2.06 (m, 8H), 1.61 (d, J = 11.8 Hz, 2H), 1.04 (s, 9H).HRMS (ESI) m/z: calcd for C₆₆H₇₇N₁₀O₆S⁺ [M + H]⁺, 1137.5743; found, 1137.6353. 15 Example 108 Synthesis of NS113-076

(2S,4R)-4-hydroxy-1-((S)-2-(5-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent-20 4-yn-1-yl)piperazin-1-yl)-5-oxopentanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-076 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 5- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-5-oxopentanoic acid. (white solid, 10.9 mg, 47%) ¹H NMR (600 MHz, Methanol-d4) δ 8.97 (d, J = 8.4 Hz, 1H), 8.71 (d, J = 5.5 Hz, 1H), 7.45 – 7.36 (m, 7H), 7.34 – 7.28 (m, 6H), 7.16 – 7.13 (m, 2H), 7.12 (s, 1H), 6.98 (s, 1H), 6.93 – 6.89 (m, 1H), 5.55 (s, 2H), 4.76 (d, J = 15.2 Hz, 1H), 4.60 (s, 1H), 4.54 (dd, J = 9.3, 7.6 Hz, 1H), 4.49-4.43 (m, 3H), 4.38-4.33 (m, 1H), 4.24 (d, J = 15.5 Hz, 1H), 3.99 (t, J = 7.0 Hz, 2H), 3.91 (d, J = 11.0 Hz, 2H), 3.81 – 3.70 (m, 4H), 3.65 (d, J = 11.8 Hz, 2H), 2.98 – 2.92 (m, 2H), 2.53 (d, J = 7.5 Hz, 1H), 2.47 (s, 3H), 2.38 (t, J = 7.3 Hz, 2H), 2.27 (q, J = 7.5, 7.1 Hz, 2H), 2.22 – 2.07 (m, 8H), 1.95 (q, J = 7.2 Hz, 2H), 1.61 (q, J = 12.4, 10.9 Hz, 2H), 1.04 (s, 9H). HRMS (ESI) m/z: calcd for C₆₇H₇₉N₁₀O₆S⁺ [M + H]⁺, 1151.5899; found, 1151.7899. Example 109 Synthesis of NS113-077

(2S,4R)-4-hydroxy-1-((S)-2-(6-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent- 4-yn-1-yl)piperazin-1-yl)-6-oxohexanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-077 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 6- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexanoic acid. (white solid, 10.7 mg, 46%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.94 (s, 1H), 8.72 (d, J = 2.7 Hz, 1H), 7.48 – 7.43 (m, 2H), 7.42 – 7.37 (m, 4H), 7.34 – 7.26 (m, 5H), 7.16 (t, J = 8.8 Hz, 2H), 7.11 (s, 1H), 7.03 (s, 1H), 6.90 (d, J = 7.8 Hz, 1H), 5.56 (s, 2H), 4.77 (d, J = 7.5 Hz, 1H), 4.64 – 4.60 (m, 1H), 4.58 – 4.44 (m, 4H), 4.36 (d, J = 15.4 Hz, 1H), 4.25 (d, J = 14.3 Hz, 1H), 4.01 (dd, J = 20.5, 6.9 Hz, 2H), 3.96 – 3.67 (m, 7H), 3.64 (d, J = 8.2 Hz, 2H), 2.94 (d, J = 7.2 Hz, 2H), 2.48 (d, J = 9.9 Hz, 5H), 2.33-2.27 (m, 4H), 2.23 – 1.97 (m, 8H), 1.72 – 1.55 (m, 6H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₆₈H₈₁N₁₀O₆S⁺ [M + H]⁺, 1165.6056; found, 1165.6952. Example 110 Synthesis of NS113-078

10 (2S,4R)-4-hydroxy-1-((S)-2-(7-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent- 4-yn-1-yl)piperazin-1-yl)-7-oxoheptanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-078 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 7- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-7-oxoheptanoic acid. (white solid, 11.8 mg, 51%) ¹H NMR (600 MHz, Methanol-d4) δ 8.95 (s, 1H), 8.72 (s, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.42 – 7.38 (m, 5H), 7.34 – 7.28 (m, 6H), 7.16 – 7.13 (m, 2H), 7.11 (s, 1H), 6.98 (s, 1H), 6.92 (d, J = 6.4 Hz, 1H), 5.56 (s, 2H), 4.78 – 4.74 (m, 1H), 4.63 (s, 1H), 4.57 – 4.45 (m, 4H), 4.37 (d, J = 15.5 Hz, 1H), 4.26 (d, J = 14.2 Hz, 1H), 4.03 – 3.97 (m 2H) 388 (d J = 111 Hz 1H) 385 – 369 (m 6H) 364 (d J = 123 Hz 2H) 294 (t, J = 7.6 Hz, 2H), 2.48 (s, 5H), 2.33 – 2.25 (m, 4H), 2.21 – 2.08 (m, 8H), 1.69 – 1.59 (m, 6H), 1.41 (t, J = 7.6 Hz, 2H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C69H83N10O6S⁺ [M + H]⁺, 1179.6212; found, 1179.5511. Example 111 Synthesis of NS113-079

(2S,4R)-4-hydroxy-1-((S)-2-(8-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent- 4-yn-1-yl)piperazin-1-yl)-8-oxooctanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-079 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 8- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-8-oxooctanoic acid. (white solid, 11.2 mg, 47%) ¹H NMR (600 MHz, Methanol-d4) δ 8.95 (s, 1H), 8.72 (s, 1H), 7.47 (d, J = 7.9 Hz, 2H), 7.43 – 7.41 (m, 2H), 7.40 – 7.36 (m, 4H), 7.33 – 7.28 (m, 5H), 7.16 – 7.13 (m, 2H), 7.10 (s, 1H), 6.97 (s, 1H), 6.92 (d, J = 5.9 Hz, 1H), 5.56 (s, 2H), 4.78 – 4.73 (m, 1H), 4.64 (s, 1H), 4.58 – 4.51 (m, 2H), 4.50 – 4.44 (m, 2H), 4.37 (d, J = 15.5 Hz, 1H), 4.25 (d, J = 13.8 Hz, 1H), 4.01 (t, J = 8.4 Hz, 2H), 3.90 (d, J = 11.0 Hz, 1H), 3.85 – 3.68 (m, 6H), 3.64 (d, J = 12.6 Hz, 2H), 2.94 (d, J = 7.8 Hz, 2H), 2.50 – 2.46 (m, 5H), 2.32 – 2.24 (m, 4H), 2.22 – 2.08 (m, 8H), 1.65-1.61 (m, 6H), 1.43 – 1.36 (m, 4H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₇₀H₈₅N₁₀O₆S⁺ [M + H]⁺, 1193.6369; found, 1193.4574. Example 112 Synthesis of NS113-080

(2S,4R)-4-hydroxy-1-((S)-2-(9-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)pent- 4-yn-1-yl)piperazin-1-yl)-9-oxononanamido)-3,3-dimethylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-080 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 3 and 9- (((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin- 1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-9-oxononanoic acid. (white solid, 11.5 mg, 48%) ¹H NMR (600 MHz, Methanol-d4) δ 9.00 (s, 1H), 8.71 (s, 1H), 7.49 – 7.46 (m, 2H), 7.43 – 7.41 (m, 2H), 7.42-7.36 (m, 4H), 7.35 – 7.30 (m, 4H), 7.19 (dt, J = 7.8, 1.4 Hz, 1H), 7.15 – 7.13 (m, 2H), 7.11 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 1.8 Hz, 1H), 6.81- 6.77 (m, 1H), 5.45 (s, 2H), 4.65 (s, 1H), 4.59 – 4.52 (m, 2H), 4.51 – 4.43 (m, 2H), 4.36 (d, J = 15.5 Hz, 1H), 3.90 – 3.87 (m, 1H), 3.81 – 3.69 (m, 6H), 3.61 – 3.56 (m, 12H), 3.23 (t, J = 6.7 Hz, 2H), 2.58-2.54 (m, 1H), 2.50 – 2.45 (m, 4H), 2.41 (dt, J = 19.3, 6.4 Hz, 4H), 2.23 – 2.07 (m, 8H), 1.66 – 1.57 (m, 6H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₇₁H₈₇N₁₀O₆S⁺ [M + H]⁺, 1207.6525; found, 1207.6648. Example 113 Synthesis of NS113-081

(2S,4R)-4-hydroxy-1-((S)-2-(10-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)pent-4-yn-1-yl)piperazin-1-yl)-10-oxodecanamido)-3,3- dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-081 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 3 and 10-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-10- oxodecanoic acid. (white solid, 12.1 mg, 50%) ¹H NMR (600 MHz, Methanol-d4) δ 8.96 (s, 1H), 8.72 (s, 1H), 7.48 – 7.46 (m, 2H), 7.43 – 7.41 (m, 2H), 7.40 – 7.36 (m, 4H), 7.33 – 7.29 (m, 5H), 7.16 – 7.13 (m, 2H), 7.09 (d, J = 2.7 Hz, 1H), 6.97 (s, 1H), 6.92 (dd, J = 6.0, 1.9 Hz, 1H), 5.56 (s, 2H), 4.76 (d, J = 14.7 Hz, 1H), 4.64 (s, 1H), 4.58 – 4.52 (m, 2H), 4.51 – 4.45 (m, 2H), 4.36 (d, J = 15.5 Hz, 1H), 4.25 (d, J = 13.8 Hz, 1H), 4.00 (q, J = 7.3 Hz, 2H), 3.90 (d, J = 11.0 Hz, 1H), 3.84 – 3.69 (m, 6H), 3.63 (d, J = 12.8 Hz, 2H), 2.94 (t, J = 7.4 Hz, 2H), 2.50 – 2.47 (m, 5H), 2.31 – 2.25 (m, 4H), 2.23 – 2.09 (m, 8H), 1.66 – 1.60 (m, 6H), 1.36 (d, J = 10.6 Hz, 8H), 1.03 (s, 9H). HRMS (ESI) m/z: calcd for C₇₂H₈₉N₁₀O₆S⁺ [M + H]⁺, 1221.6682; found, 1221.7228. Example 114 Synthesis of NS113-082

(2S,4R)-4-hydroxy-1-((S)-2-(11-(4-(5-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)pent-4-yn-1-yl)piperazin-1-yl)-11-oxoundecanamido)-3,3- dimethylbutanoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. NS113-082 was synthesized following the standard procedure for preparing NS106- 033 from Intermediate 3 and 11-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11- oxoundecanoic acid. (white solid, 11.7 mg, 47%) ¹H NMR (600 MHz, Methanol-d4) δ 8.94 (s, 1H), 8.72 (s, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.43 – 7.41 (m, 2H), 7.40 – 7.36 (m, 4H), 7.33 – 7.29 (m, 5H), 7.16 – 7.13 (m, 2H), 7.09 (d, J = 2.6 Hz, 1H), 6.96 (s, 1H), 6.94 – 6.91 (m, 1H), 5.56 (s, 2H), 4.76 (d, J = 14.8 Hz, 1H), 4.64 (s, 1H), 4.58 – 4.53 (m, 2H), 4.48 (d, J = 21.8 Hz, 2H), 4.36 (d, J = 15.5 Hz, 1H), 4.25 (d, J = 13.8 Hz, 1H), 4.00 (q, J = 7.3 Hz, 2H), 3.90 (d, J = 11.0 Hz, 1H), 3.83 – 3.69 (m, 6H), 3.63 (d, J = 12.8 Hz, 2H), 2.94 (q, J = 7.0, 6.4 Hz, 2H), 2.48 (d, J = 5.3 Hz, 5H), 2.29-2.23 (m, 4H), 2.20 – 2.07 (m, 8H), 1.61 (d, J = 13.3 Hz, 6H), 1.35 (d, J = 18.4 Hz, 10H), 1.03 (d, J = 1.5 Hz, 9H). HRMS (ESI) m/z: calcd for C₇₃H₉₁N₁₀O₆S⁺ [M + H]⁺, 1235.6838; found, 1235.7313. Example 115 Synthesis of NS121-135

(3r,5r,7r)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)adamantane-1-carboxamide. NS121-135 was synthesized following the standard 5 procedure for preparing NS106-033 from Intermediate 2 and 1-adamantanecarboxylic acid. (white solid, 7.5 mg, 51%) ¹H NMR (600 MHz, Methanol-d4) δ 8.72 (s, 1H), 7.44- 7.39 (m, 4H), 7.36 – 7.29 (m, 4H), 7.22-7.18 (m, 1H), 7.17-7.14 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.83-6.74 (m, 1H), 5.46 (s, 2H), 4.44 (t, J = 11.8 Hz, 1H), 3.79 – 3.73 (m, 1H), 3.21 (t, J = 6.8 Hz, 2H), 2.39 (t, J = 6.8 Hz, 2H), 2.18-10 2.13 (m, 6H), 2.00 (s, 3H), 1.84 (d, J = 2.9 Hz, 6H), 1.77 (d, J = 12.4 Hz, 3H), 1.74 – 1.69 (m, 3H), 1.66 – 1.54 (m, 6H). HRMS (ESI) m/z: calcd for C₄₈H₅₄N₅O₂ ⁺ [M + H]⁺, 732.4272; found, 732.4295. Example 116 15 Synthesis of NS121-136

2-((3r,5r,7r)-adamantan-1-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5- yn-1-yl)acetamide. NS121-136 was synthesized following the standard procedure for20 preparing NS106-033 from Intermediate 2 and 1-adamantaneacetic acid. (white solid, 7.2 mg, 48%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.72 (s, 1H), 7.42 – 7.37 (m, 4H), 7.36 – 7.30 (m, 4H), 7.22-7.17 (m, 1H), 7.16-7.12 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (t, J = 1.7 Hz, 1H), 6.80 – 6.77 (m, 1H), 5.45 (s, 2H), 4.47 – 4.41 (m, 1H), 3.79- 3.74 (m, 1H), 3.21 (t, J = 6.6 Hz, 2H), 2.41 (t, J = 6.7 Hz, 2H), 2.23 – 2.09 (m, 6H), 1.92 (d, J = 6.3 Hz, 5H), 1.75 – 1.52 (m, 18H). HRMS (ESI) m/z: calcd for C + 49H56N5O2 [M + H]⁺, 746.4429; found, 746.4408. Example 117 Synthesis of NS121-137

3-((3r,5r,7r)-adamantan-1-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5- yn-1-yl)propanamide. NS121-137 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3-(1-adamantyl) propanoic acid. (white solid, 7.6 mg, 50%) ¹H NMR (600 MHz, Methanol-d4) δ 8.72 (s, 1H), 7.43-7.38 (m, 4H), 7.36 – 7.30 (m, 4H), 7.19 (d, J = 7.8 Hz, 1H), 7.16 – 7.13 (m, 2H), 7.11 (t, J = 7.7 Hz, 1H), 6.85 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.46 (s, 2H), 4.43 (t, J = 11.8 Hz, 1H), 3.79 – 3.74 (m, 1H), 3.20 (t, J = 6.7 Hz, 2H), 2.40 (t, J = 6.8 Hz, 2H), 2.22 – 2.11 (m, 7H), 1.94 (d, J = 18.1 Hz, 4H), 1.77 – 1.49 (m, 20H). HRMS (ESI) m/z: calcd for C₅₀H₅₈N₅O₂ ⁺ [M + H]⁺, 760.4585; found, 760.4599. Example 118 Synthesis of NS121-138

2 ((1r,3R,5S,7r) 3,5 dimethyladamantan 1 yl) N (6 (3 ((3 ((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide. NS121-138 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 2 and 3,5-dimethyl-1-adamantaneacetic acid. (white solid, 7.3 mg, 47% _{1H NMR (600 MHz, Methanol-d4) $ 8.72 (s, 1H), 7.45 – 7.37 (m, 4H), 7.36 – 7.29 (m,} _{4H), 7.20 – 7.18 (m, 1H), 7.15 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.87 (d, J = 1.9} _{Hz, 1H), 6.78 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.47 – 4.40 (m, 1H), 3.79-3.74 (m, 1H),} _{3.21 (t, J = 6.4 Hz, 2H), 2.40 (t, J = 6.7 Hz, 2H), 2.22 – 2.08 (m, 6H), 2.01 (q, J = 3.2} _{Hz, 1H), 1.96 (s, 2H), 1.68 – 1.55 (m, 6H), 1.45 (d, J = 3.1 Hz, 2H), 1.35 – 1.25 (m,} _{6H), 1.21 (d, J = 12.2 Hz, 2H), 1.13-1.09 (m, 1H), 1.05 (d, J = 12.2 Hz, 1H), 0.78 (s,} _{6H). HRMS (ESI) m/z: calcd for C51H60N5O2+ [M + H]+, 774.4742; found, 774.4749.} _{Example 119} _{Synthesis of NS121-139}

_{2-((1R,3S,5r,7r)-adamantan-2-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-} _{imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-} _{yl)methyl)phenyl)hex-5-yn-1-yl)acetamide. NS121-139 was synthesized following} _{the standard procedure for preparing NS106-033 from Intermediate 2 and 2-} _{adamantaneacetic acid. (white solid, 6.7 mg, 45%) 1H NMR (600 MHz, Methanol-d4)} _{δ 8.72 (s, 1H), 7.45 – 7.37 (m, 4H), 7.37 – 7.29 (m, 4H), 7.22-7.18 (m, 1H), 7.16 – 7.13} _{(m, 2H), 7.11 (t, J = 7.7 Hz, 1H), 6.86 (t, J = 1.8 Hz, 1H), 6.79 (d, J = 7.7 Hz, 1H), 5.46} _{(s, 2H), 4.47 – 4.41 (m, 1H), 3.80 – 3.74 (m, 1H), 3.22 (t, J = 6.7 Hz, 2H), 2.39 (t, J =} _{6.8 Hz, 2H), 2.34 (d, J = 7.8 Hz, 2H), 2.24 – 2.09 (m, 7H), 1.95 (d, J = 12.8 Hz, 2H),} _{1.84 (d, J = 12.5 Hz, 3H), 1.81 – 1.73 (m, 5H), 1.69 – 1.54 (m, 10H). HRMS (ESI) m/z:} _{calcd for C49H56N5O2+ [M + H]+, 746.4429; found, 746.4349.} _{Example 120} _{Synthesis of NS121-140}

N-(((3r,5r,7r)-adamantan-1-yl)methyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamide. NS121-140 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 1- adamantanemethylamine. (white solid, 7.6 mg, 51%) ¹H NMR (600 MHz, Methanol- d4) δ 8.72 (s, 1H), 7.43-7.38 (m, 4H), 7.36 – 7.29 (m, 4H), 7.21 – 7.17 (m, 1H), 7.16 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.7 Hz, 1H), 6.79 (d, J = 7.7 Hz, 1H), 5.45 (s, 2H), 4.46 – 4.41 (m, 1H), 3.80 – 3.74 (m, 1H), 2.87 (s, 2H), 2.41 (t, J = 7.0 Hz, 2H), 2.26 (t, J = 7.4 Hz, 2H), 2.18-2.15 (m, 6H), 1.92 (s, 3H), 1.80 – 1.59 (m, 12H), 1.50 (d, J = 2.9 Hz, 6H). HRMS (ESI) m/z: calcd for C₄₉H₅₆N₅O₂ ⁺ [M + H]⁺, 746.4429; found, 746.4411. Example 121 Synthesis of NS121-141 N

-(2-((3r,5r,7r)-adamantan-1-yl)ethyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamide. NS121-141 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 2-(1- adamantyl)ethanamine hydrochloride. (white solid, 7.0 mg, 46%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.72 (s, 1H), 7.47 – 7.37 (m, 4H), 7.36 – 7.27 (m, 4H), 7.21 – 7.17 (m, 1H), 7.16 – 7.13 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.45 (s, 2H), 4.46 – 4.42 (m, 1H), 3.79 – 3.74 (m, 1H), 3.18 (t, J = 7.2 Hz, 2H), 2.40 (t, J = 7.0 Hz, 2H), 2.19-2.15 (m, 8H), 1.90 (d, J = 12.8 Hz, 2H), 1.84 (d, J = 12.2 Hz, 3H), 1.78 – 1.32 (m, 18H). HRMS (ESI) m/z: calcd for C₅₀H₅₈N₅O₂ ⁺ [M + H]⁺, 760.4585; found, 760.4597. Example 122 Synthesis of NS121-142

N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)-7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)- 4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamide. NS121-142 was synthesized following the standard procedure for preparing NS106-033 from Intermediate 1 and 4-(1- adamantyl)aniline. (white solid, 7.0 mg, 43%) ¹H NMR (600 MHz, Methanol-d₄) δ 8.70 (s, 1H), 7.49 – 7.45 (m, 2H), 7.42 – 7.35 (m, 4H), 7.35 – 7.24 (m, 6H), 7.19 (d, J = 7.7 Hz, 1H), 7.14 – 7.07 (m, 3H), 6.87 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 5.44 (s, 2H), 4.43- 4.35 (m, 1H), 3.77-3.73 (m, 1H), 2.44-2.41 (m, 4H), 2.22 – 2.04 (m, 9H), 1.91 (d, J = 2.9 Hz, 6H), 1.88 – 1.76 (m, 8H), 1.67 – 1.55 (m, 4H). HRMS (ESI) m/z: calcd for C₅₄H₅₈N₅O₂ ⁺ [M + H]⁺, 808.4585; found, 808.4577.

Certain compounds disclosed herein have the structures shown in Table 1. Table 1

Compounds corresponding to Examples 4-122 have been synthesized and are provided with a Compound ID in Table 1. Compounds in Table 2 corresponding to Examples 123 - 144 are not provided with a Compound ID. These compounds may be synthesized according to the schemes set forth above. As used herein, in case of discrepancy between the structure and chemical name provided for a particular compound, the given structure shall control. Example 145 PNC-dependent and independent cell growth inhibition by Metarrestin-based PROTACs (Fig.1). Inhibitory effect of degraders was tested in serial dilution in different cell lines. It was shown that both VHL-recruiting and CRBN-recruiting PROTACs showed better inhibitory profile compared to parent compound in both low and high PNC-cell lines (Fig.1). Example 146 Degradation of eEF1A2 by Metarrestin-based PROTACs (Fig.2). NS106-70 induced eEF1A2 degradation in PC-3M, PANC1 and MDA-MB-231 cell lines in a concentration-dependent manner (Fig. 2). Furthermore, NS106-70 almost fully degraded eEF1A2 at 5 PM in MDA-MB-231 cells despite that this cell line having very low PNC, suggesting that this eEF1A2 PROTAC degrader can act in a PNC- independent fashion. We also observed that similar to VHL-recruiting PROTACs, our CRBN-recruiting PROTAC, NS106-78, induced eEF1A2 degradation in PANC1 and MDA-MB-231 cells in a concentration-dependent manner (Fig.2). Example 147 Degradation kinetics of eEF1A2 via Metarrestin-based degraders (Fig.3) NS106-70 induced significant eEF1A2 degradation at 24 and 48 h while our NS106-78 induced eEF1A2 degradation at 48 h (Fig. 3). We also designed and synthesized a negative control of NS106-70, NS106-149, which is a very close analog of NS106-70. NS106-179 was designed to bind eEF1A2 with a similar affinity as NS106-70, but not bind the E3 ligase VHL. We observed that NS106-149 did not degrade eEF1A2 in PANC1 and MDA-MB-231 cells (Fig. 3), suggesting that the eEF1A2 degradation induced by NS106-70 is mediated by the ubiquitin-proteasome pathway. Example 148 Degradation of eEF1A2 by Metarrestin-based PROTACs (Fig. 4) and their cytotoxicity (Table 3). Significant eEF1A2 degradation at 24 and cyctoxicity at 72 were observed by treatment with several degraders in PANC-1 cells. TABLE 3 Compound Code PANC1 Cell Line GI₅₀ (µM) NS106-040 >25 NS106-041 >25 NS106-042 >25 NS106-043 >25 NS106-044 7.3 ± 2.1 NS106-045 7.4 ± 1.3 NS106046 >25 NS106-048 >25 NS106-049 >25 NS113-044 >25 NS113-045 >25 NS113-046 13.6 ± 2.2 NS113-047 5.7 ± 1.3 NS113-048 8.1 ± 3.5 NS113-049 8.1 ± 2.8 NS113-050 >25 NS113-051 >25 NS113-052 >25 NS113-053 >25 NS113-054 >25 NS113-055 >25 NS113-056 >25 NS113-057 7.4 ± 1.8 NS113-058 8.2 ± 1.5 NS113-059 8.5 ± 1.9 NS113-060 >25 NS113-061 >25 GI₅₀ values, 72 hr treatment in PANC1 cells. represented by mean value ± SD were obtained from at least two independent experiments Materials And Methods: General Chemistry Methods For the synthesis of intermediates and examples (1-122) below, HPLC spectra for all compounds were acquired using an Agilent 1200 Series system with DAD detector. Chromatography was performed on a 2.1×150 mm Zorbax 300SB-C185 µm column with water containing 0.1% formic acid as solvent A and acetonitrile containing 0.1% formic acid as solvent B at a flow rate of 0.4 ml/min. The gradient program was as follows: 1% B (0%1 min), 1%99% B (1%4 min), and 99% B (4%8 min). High-resolution mass spectra (HRMS) data were acquired in positive ion mode using an Agilent G1969A API-TOF with an electrospray ionization (ESI) source. Nuclear Magnetic Resonance (NMR) spectra were acquired on a Bruker DRX-600 spectrometer with 600 shifts are reported in (δ). Preparative HPLC was performed on Agilent Prep 1200 series with UV detector set to 254 nm. Samples were injected onto a Phenomenex Luna 250 x 30 mm, 5 µm, C18 column at room temperature. The flow rate was 40 ml/min. A linear gradient was used with 10% (or 50%) of MeOH (A) in H₂O (with 0.1 % TFA) (B) to 100% of MeOH (A). HPLC was used to establish the purity of target compounds. All final compounds had > 95% purity using the HPLC methods described above. Cell Culture MDA-MB-231 (ATCC) and PANC1 (ATCC) were cultivated in DMEM and PC-3M (Elabscience) cells were cultivated in RPMI-1640 medium supplemented with 10% FBS, 100 units/mL of penicillin, and 100 &g/mL of streptomycin. Cell Viability PNC-dependent PC-3M and PNC-independent MDA-MB-231 cells were seeded at 5x10⁴ cells/mL density into 96-well microplates (Thermo Scientific) and treated with DMSO or the indicated compounds with serial dilution in triplicates for 5 days. Metarrestin was used as a positive control. Cell viability was measured using WST-8 reagent (CK04, Dojindo). Briefly, ten microliters of WST-8 reagent was added to each well, and the plates were kept in an incubator at 37 °C for 3 h in the dark. Absorbance signals for WST-8 were read at 450 nm with 650 nm as reference performed with Infinite F PLEX plate reader (TECAN, Morrisville, NC). GI50 values were analyzed using GraphPad Prism 8. Western Blotting Cells were lysed on ice for 30 min with the lysis buffer (50 mM Tris pH 7.4, 1% IGEPAL CA-630, 150 mM NaCl, 1 mM EDTA, and 1 mM AESBF), supplemented with protease and phosphatase inhibitor cocktail (A32961, Thermo Fisher Scientific). The sample was centrifuged at 12000g for 10 min at 4 °C to get supernatant as cell lysate. The primary antibodies used were eEF1A2 (16091-1-AP Proteintech) eEF1A1 (11402-1-AP, Proteintech) and Vinculin (4650S, Cell Signaling Technology). Fluorescence-labeled secondary antibodies (IRDye 800, LI-COR) and the OdysseyCLx imaging system (LI-COR) were used to obtain protein signals, which were then analyzed by Image Studio Lite software (LI-COR). References [1] G. J. Browne, C. G. Proud, Eur J Biochem 2002, 269, 5360-5368. [2] A. Khalyfa, D. Bourbeau, E. Chen, E. Petroulakis, J. Pan, S. Xu, E. Wang, J Biol Chem 2001, 276, 22915-22922. [3] H. Duanmin, X. Chao, Z. Qi, Hepatogastroenterology 2013, 60, 870-875. [4] C. Xu, D. M. Hu, Q. Zhu, Clin Exp Metastasis 2013, 30, 933-944. [5] H. Cao, Q. Zhu, J. Huang, B. Li, S. Zhang, W. Yao, Y. Zhang, Biochem Biophys Res Commun 2009, 380, 11-16. [6] A. Losada, M. J. Munoz-Alonso, M. Martinez-Diez, F. Gago, J. M. Dominguez, J. F. Martinez-Leal, C. M. Galmarini, Br J Cancer 2018, 119, 1410-1420. [7] R. Pellegrino, D. F. Calvisi, O. Neumann, V. Kolluru, J. Wesely, X. Chen, C. Wang, T. Wuestefeld, S. Ladu, N. Elgohary, J. L. Bermejo, B. Radlwimmer, M. Zornig, L. Zender, F. Dombrowski, M. Evert, P. Schirmacher, T. Longerich, Hepatology 2014, 59, 1886-1899. [8] S. Liu, S. Hausmann, S. M. Carlson, M. E. Fuentes, J. W. Francis, R. Pillai, S. M. Lofgren, L. Hulea, K. Tandoc, J. Lu, A. Li, N. D. Nguyen, M. Caporicci, M. P. Kim, A. Maitra, H. Wang, Wistuba, II, J. A. Porco, Jr., M. C. Bassik, J. E. Elias, J. Song, I. Topisirovic, C. Van Rechem, P. K. Mazur, O. Gozani, Cell 2019, 176, 491-504 e421. [9] M. E. Jakobsson, J. M. Malecki, L. Halabelian, B. S. Nilges, R. Pinto, S. Kudithipudi, S. Munk, E. Davydova, F. R. Zuhairi, C. H. Arrowsmith, A. Jeltsch, S. A. Leidel, J. V. Olsen, P. O. Falnes, Nat Commun 2018, 9, 3411. [10] K. J. Frankowski, C. Wang, S. Patnaik, F. J. Schoenen, N. Southall, D. Li, Y. Teper, W. Sun, I. Kandela, D. Hu, C. Dextras, Z. Knotts, Y. Bian, J. Norton, S. Titus, M. A. Lewandowska, Y. Wen, K. I. Farley, L. M. Griner, J. Sultan, Z. Meng, M. Zhou, T. Vilimas, A. S. Powers, S. Kozlov, K. Nagashima, H. S. Quadri, M. Fang, C. Long, O. Khanolkar, W. Chen, J. Kang, H. Huang, E. Chow, E. Goldberg, C. Feldman, R. Xi, H. R. Kim, G. Sahagian, S. J. Baserga, A. Mazar, M. Ferrer, W. Zheng, A. Shilatifard, J. Aube, U. Rudloff, J. J. Marugan, S. Huang, Sci Transl Med 2018, 10. [11] M. J. Kanis, W. Qiang, M. Pineda, K. P. Maniar, J. J. Kim, Gynecol Oncol Res Pract 2018, 5, 7. [12] M. J. Kanis, W. Qiang, J. R. Lurain, S. Huang, J. J. Kim, Gynecol Oncol 2015, 139, 190. [13] ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2020 January 10- . Identifier NCT04222413, Metarrestin (ML-246) in Subjects with Metastatic Solid Tumors. [14] M. Bourdi, U. Rudloff, S. Patnaik, J. Marugan, P. S. Terse, Regul Toxicol Pharmacol 2020, 116, 104716. [15] M. Schapira, M. F. Calabrese, A. N. Bullock, C. M. Crews, Nat Rev Drug Discov 2019, 18, 949-963. [16] A. C. Lai, C. M. Crews, Nat Rev Drug Discov 2017, 16, 101-114. [17] D. P. Bondeson, B. E. Smith, G. M. Burslem, A. D. Buhimschi, J. Hines, S. Jaime-Figueroa, J. Wang, B. D. Hamman, A. Ishchenko, C. M. Crews, Cell Chem Biol 2018, 25, 78-87 e75. [18] H. T. Huang, D. Dobrovolsky, J. Paulk, G. Yang, E. L. Weisberg, Z. M. Doctor, D. L. Buckley, J. H. Cho, E. Ko, J. Jang, K. Shi, H. G. Choi, J. D. Griffin, Y. Li, S. P. Treon, E. S. Fischer, J. E. Bradner, L. Tan, N. S. Gray, Cell Chemical Biology 2018, 25, 88. [19] Y. H. Sun, X. W. Zhao, N. Ding, H. Y. Gao, Y. Wu, Y. Q. Yang, M. Zhao, J. Hwang, Y. Q. Song, W. L. Liu, Y. Rao, Cell Res 2018, 28, 779-781. [20] D. P. Bondeson, A. Mares, I. E. Smith, E. Ko, S. Campos, A. H. Miah, K. E. Mulholland, N. Routly, D. L. Buckley, J. L. Gustafson, N. Zinn, P. Grandi, S. Shimamura, G. Bergamini, M. Faelth-Savitski, M. Bantscheff, C. Cox, D. A. Gordon, R. R. Willard, J. J. Flanagan, L. N. Casillas, B. J. Votta, W. den Besten, K. Famm, L. Kruidenier, P. S. Carter, J. D. Harling, I. Churcher, C. M. Crews, Nat Chem Biol 2015, 11, 611-617. [21] K. Raina, J. Lu, Y. M. Qian, M. Altieri, D. Gordon, A. M. K. Rossi, J. Wang, X. Chen, H. Q. Dong, K. Siu, J. D. Winkler, A. P. Crew, C. M. Crews, K. G. Coleman, P Natl Acad Sci USA 2016, 113, 7124-7129. [22] B. Zhou, J. Hu, F. Xu, Z. Chen, L. Bai, E. Fernandez-Salas, M. Lin, L. Liu, C. Y. Yang, Y. Zhao, D. McEachern, S. Przybranowski, B. Wen, D. Sun, S. Wang, J Med Chem 2018, 61, 462-481. [23] D. L. Buckley, C. M. Crews, Angew. Chem. Int. Ed. Engl.2014, 53, 2312- 2330. [24] (a) P. P. Chamberlain, A. Lopez-Girona, K. Miller, G. Carmel, B. Pagarigan, B. Chie-Leon, E. Rychak, L. G. Corral, Y. J. Ren, M. Wang, M. Riley, S. L. Delker, T. Ito, H. Ando, T. Mori, Y. Hirano, H. Handa, T. Hakoshima, T. O. Daniel, B. E. Cathers, Nat. Struct. Mol. Biol.2014, 21, 803-809; (b) E. S. Fischer, K. Bohm, J. R. Lydeard, H. Yang, M. B. Stadler, S. Cavadini, J. Nagel, F. Serluca, V. Acker, G. M. Lingaraju, R. B. Tichkule, M. Schebesta, W. C. Forrester, M. Schirle, U. Hassiepen, J. Ottl, M. Hild, R. E. Beckwith, J. W. Harper, J. L. Jenkins, N. H. Thoma, Nature 2014, 512, 49-53; (c) T. Ito, H. Ando, T. Suzuki, T. Ogura, K. Hotta, Y. Imamura, Y. Yamaguchi, H. Handa, Science 2010, 327, 1345-1350; (d) G. E. Winter, D. L. Buckley, J. Paulk, J. M. Roberts, A. Souza, S. Dhe-Paganon, J. E. Bradner, Science 2015, 348, 1376- 1381. [25] (a) D. L. Buckley, J. L. Gustafson, I. Van Molle, A. G. Roth, H. S. Tae, P. C. Gareiss, W. L. Jorgensen, A. Ciulli, C. M. Crews, Angew. Chem. Int. Ed. Engl. 2012, 51, 11463-11467; (b) D. L. Buckley, I. Van Molle, P. C. Gareiss, H. S. Tae, J. Michel, D. J. Noblin, W. L. Jorgensen, A. Ciulli, C. M. Crews, J. Am. Chem. Soc.2012, 134, 4465-4468; (c) C. Galdeano, M. S. Gadd, P. Soares, S. Scaffidi, I. Van Molle, I. Birced, S. Hewitt, D. M. Dias, A. Ciulli, J. Med. Chem.2014, 57, 8657-8663; (d) M. Zengerle, K. H. Chan, A. Ciulli, ACS Chem. Biol.2015, 10, 1770-1777. [26] (a) D. L. Buckley, K. Raina, N. Darricarrere, J. Hines, J. L. Gustafson, I. E. Smith, A. H. Miah, J. D. Harling, C. M. Crews, ACS Chem. Biol.2015, 10, 1831-1837; (b) A. C. Lai, M. Toure, D. Hellerschmied, J. Salami, S. Jaime- Figueroa, E. Ko, J. Hines, C. M. Crews, Angew. Chem. Int. Ed. Engl.2016, 55, 807-810; (c) J. Lu, Y. Qian, M. Altieri, H. Dong, J. Wang, K. Raina, J. Hines, J. D. Winkler, A. P. Crew, K. Coleman, C. M. Crews, Chemistry & biology 2015, 22, 755-763. [27] T. Xie, S. M. Lim, K. D. Westover, M. E. Dodge, D. Ercan, S. B. Ficarro, D. Udayakumar, D. Gurbani, H. S. Tae, S. M. Riddle, T. Sim, J. A. Marto, P. A. Janne, C. M. Crews, N. S. Gray, Nat. Chem. Biol.2014, 10, 1006-1012.

Claims

CLAIMS 1. A bifunctional compound comprising a degradation/disruption tag, conjugated to an eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) inhibitor, via a linker. 2. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 1:

FORMULA 1 wherein the linker moiety of the bifunctional compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; R¹ is selected from the group consisting of:

O O O O HO HO HO HO

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)₂R¹¹, S(O)₂NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1- C8 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C8 cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl optionally substituted 3-8 membered cycloalkyl optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁- C₈ alkylamino C₁-C₈ alkyl; and enantiomers and pharmaceutically acceptable salts thereof. 3. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 2:

Wherein the linker moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; R¹ is selected from the group consisting of:

O O O O HO HO HO HO

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)₂R¹¹, S(O)₂NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1- C8 alkyl, optionally substituted C₃-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C8 cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W, Q, and Z, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C1- C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 4. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 3:

FORMULA 3 wherein, the Linker moiety of the bivalent compound is attached to N as indicated by the dotted line; X is selected from NH or O or S; Z is selected from N or CH; R¹ is selected from the group consisting of:

O O O O HO HO HO HO

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)₂R¹¹, S(O)₂NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1- C8 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C8 cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl optionally substituted C₁-C₈ alkoxy optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C1- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 5. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 4:

FORMULA 4 wherein, the linker moiety of the bivalent compound is attached to N as indicated by the dotted line; X is selected from NH or O or S; Z is selected from N or CH; R¹ is selected from the group consisting of:

O O O O HO HO HO HO

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO₂, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)₂R¹¹, S(O)₂NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1- C8 alkyl, optionally substituted C₃-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C8 cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl optionally substituted C₁-C₈ alkoxy optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 6. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 5:

10 FORMULA 5 wherein the linker moiety of the bivalent compound is attached to Z as indicated by the dotted line; X is selected from NH or O or S; R¹ is selected from the group consisting of:

R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, at each occurrence, are independently selected from hydrogen, halogen, oxo, Ph, CN, NO2, OR¹¹, SR¹¹, NR¹¹R¹², C(O)R¹¹, C(O)OR¹¹, C(O)NR¹¹R¹², S(O)R¹¹, S(O)2R¹¹, S(O)2NR¹¹R¹², NR¹³C(O)OR¹¹, NR¹³C(O)R¹¹, NR¹³C(O)NR¹¹R¹², NR¹³S(O)R¹¹, NR¹³S(O)₂R¹¹, NR¹³S(O)₂NR¹¹R¹² optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1-C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R¹¹, R¹², and R¹³ are independently selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxyC1-C8 alkyl, optionally substituted C1-C8 alkylaminoC1- C8 alkyl, optionally substituted C₃-C10 cycloalkyl, optionally substituted 3-20 membered heterocyclyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted aryl, and optionally substituted heteroaryl, or R¹¹ and R¹², R¹¹ and R¹³, R¹² and R¹³ together with the atom to which they are connected form an optionally substituted 3-20 membered cycloalkyl or heterocyclyl ring; R¹⁷, R¹⁸, R¹⁹, and R²⁰, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃- C₈ cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted C₁-C₈ alkoxy C₁-C₈ alkyl, optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; m, n, at each occurrence, are independently selected from 0, 1, 2, 3, and 4; and W and Q, at each occurrence, are independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C1- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 7. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety of FORMULA 6:

FORMULA 6 wherein the linker moiety of the bivalent compound is attached to Z as indicated by the dotted line; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂- NH-CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂- NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 8. The bifunctional compound of claim 1, wherein the eEF1A2 inhibitor comprises a moiety according to FORMULA 6A or FORMULA 6B:

FORMULA 6B wherein the linker moiety of the bivalent compound is attached to Z as indicated by the dotted line; Z at each occurrence, is independently selected from null, CO, CO2, CH₂, NH, NH- CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH-CH₂- CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CR²¹R²², C(O)NR²¹ , C(S)NR²¹, O, S, SO, SO₂, SO₂NR²¹, NR²¹, NR²¹CO, NR²¹CONR²², NR²¹C(S), optionally substituted C1-C8 alkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkoxy C1-C8 alkyl, optionally substituted C1-C8 haloalkyl, optionally substituted C1-C8 hydroxyalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C3-C13 fused heterocyclyl, optionally substituted C3-C13 bridged cycloalkyl, optionally substituted C3-C13 bridged heterocyclyl, optionally substituted C3-C13 spiro cycloalkyl, and optionally substituted C3-C13 spiro heterocyclyl; wherein R²¹ and R²² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl optionally substituted 3-8 membered cycloalkyl optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁- C8 alkylamino C₁-C₈ alkyl; and pharmaceutically acceptable salts thereof. 9. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to FORMULAE 12A, 12B, 12C and 12D:

FORMULA 12A FORMULA 12B FORMULA 12C FORMULA 12D, wherein V, W, and X are independently selected from CR² and N; 15 Y is selected from CO, CR³R⁴, and N=N; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C₁-C₁₀ alkylene, optionally substituted C₁-C₁₀ alkenylene, optionally substituted C₁-C₁₀ alkynylene, optionally substituted 3-10 membered carbocyclyl, optionally substituted 4-10 membered heterocyclyl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferly, Z is selected from null, CH₂, CH=CH, C C, NH and O; R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl. 10. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to one of FORMULAE 12E, 12F, 12G, 12H, and 12I: 15

FORMULA 12E FORMULA 12F FORMULA 12G

FORMULA 12H FORMULA 12I wherein U, V, W, and X are independently selected from CR² and N; Y is selected from CR³R⁴, NR³ and O; preferably, Y is selected from CH₂, NH, NCH₃ and O; Z is selected from null, CO, CR⁵R⁶, NR⁵, O, optionally substituted C₁-C₁₀ alkylene, optionally substituted C₁-C₁₀ alkenylene, optionally substituted C₁-C₁₀ 4-10 membered heterocyclyl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, optionally substituted C₃-C₁₃ spiro heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; preferably, Z is selected from n_{ull, CH2, CH=CH, C} ^{C, NH and O;} R¹, and R² are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; R³, and R⁴ are independently selected from hydrogen, halogen, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R³ and R⁴ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl; and R⁵ and R⁶ are independently selected from null, hydrogen, halogen, oxo, hydroxyl, amino, cyano, nitro, optionally substituted C₁-C₆ alkyl, optionally substituted 3 to 6 membered carbocyclyl, and optionally substituted 4 to 6 membered heterocyclyl; or R⁵ and R⁶ together with the atom to which they are connected form a 3-6 membered carbocyclyl, or 4-6 membered heterocyclyl. 11. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to FORMULA 13A: 25

FORMULA 13A, wherein R¹ and R² are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C1- C8 haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; and R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)C₃-C7 cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl, optionally substituted C(O)OC₁-C₈ hydroxyalkyl, optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC1- C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C₇ cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC₁-C₈ hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)NC₃-C₇ cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)₂, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)2.

12. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to FORMULAE 13B, 13C, 13D, 13E and 13F: 5

FORMULA 13B FORMULA 13C

FORMULA 13D FORMULA 13E FORMULA 13F wherein R¹ and R² are independently selected from hydrogen, halogen, OH, NH₂, CN, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ aminoalkyl, optionally substituted C₁-C₈alkylaminoC1- C8alkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; (preferably, R¹ is selected from iso-propyl or tert-butyl; and R² is selected from hydrogen or methyl); R³ is hydrogen, optionally substituted C(O)C₁-C₈ alkyl, optionally substituted C(O)C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)C₁-C₈ haloalkyl, optionally substituted C(O)C₁-C₈ hydroxyalkyl, optionally substituted C(O)C₁-C₈ aminoalkyl, optionally substituted C(O)C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)C₃- C7 cycloalkyl, optionally substituted C(O)(3-7 membered heterocyclyl), optionally substituted C(O)C₂-C₈ alkenyl, optionally substituted C(O)C₂-C₈ alkynyl, optionally substituted C(O)OC₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C(O)OC₁-C₈ haloalkyl optionally substituted C(O)OC₁-C₈ hydroxyalkyl optionally substituted C(O)OC₁-C₈ aminoalkyl, optionally substituted C(O)OC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)OC₃-C7 cycloalkyl, optionally substituted C(O)O(3-7 membered heterocyclyl), optionally substituted C(O)OC₂-C₈ alkenyl, optionally substituted C(O)OC₂-C₈ alkynyl, optionally substituted C(O)NC₁-C₈alkoxyC₁- C8alkyl, optionally substituted C(O)NC₁-C₈ haloalkyl, optionally substituted C(O)NC1- C8 hydroxyalkyl, optionally substituted C(O)NC₁-C₈ aminoalkyl, optionally substituted C(O)NC₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted C(O)NC₃-C7 cycloalkyl, optionally substituted C(O)N(3-7 membered heterocyclyl), optionally substituted C(O)NC₂-C₈ alkenyl, optionally substituted C(O)NC₂-C₈ alkynyl, optionally substituted P(O)(OH)₂, optionally substituted P(O)(OC₁-C₈ alkyl)₂, and optionally substituted P(O)(OC₁-C₈ aryl)2; and R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO2R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC1- C8alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁴ and R⁵; R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring; Ar is selected from aryl and heteroaryl, each of which is optionally substituted with one or more substituents independently selected from F, Cl, CN, NO2, OR⁸, NR⁸R⁹, COR⁸, CO2R⁸, CONR⁸R⁹, SOR⁸, SO₂R⁸, SO₂NR⁹R¹⁰, NR⁹COR¹⁰, NR⁸C(O)NR⁹R¹⁰, NR⁹SOR¹⁰, NR⁹SO₂R¹⁰, optionally substituted C₁-C₆ alkyl, optionally substituted C₁-C₆ alkoxyalkyl, optionally substituted C₁-C₆ haloalkyl, optionally substituted C₁-C₆ hydroxyalkyl optionally substituted C₁-C₆alkylaminoC₁- C₆alkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₆ alkenyl, optionally substituted C₂-C₆ alkynyl, optionally substituted aryl, and optionally substituted C₄-C₅ heteroaryl; wherein R⁸, R⁹, and R¹⁰ are independently selected from null, hydrogen, optionally substituted C₁-C₆ alkyl, optionally substituted C₂-C₆ alkenyl, optionally substituted C₂- C₆ alkynyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁸ and R⁹; R⁹ and R¹⁰ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring. 13. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to FORMULA 14A:

FORMULA 14A wherein 20 V, W, X, and Z are independently selected from CR⁴ and N; R¹, R², R³, and R⁴ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C7 cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl.

14. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from a moiety according to FORMULA 14B: 5

FORMULA 14B, wherein R¹, R², and R³ are independently selected from hydrogen, halogene, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₃-C₇ cycloalkyl, optionally substituted 3-7 membered heterocyclyl, optionally substituted C₂-C₈ alkenyl, and optionally substituted C₂-C₈ alkynyl; R⁴ and R⁵ are independently selected from hydrogen, COR⁶, CO₂R⁶, CONR⁶R⁷, SOR⁶, SO₂R⁶, SO₂NR⁶R⁷, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl, optionally substituted aryl-C₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R⁶ and R⁷ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C1- C₈alkylaminoC₁-C₈alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; or R⁶ and R⁷ together with the atom to which they are connected form a 4-8 membered cycloalkyl or heterocyclyl ring.

15. The bifunctional compound of any one of claims 1 - 8, wherein the degradation/disruption tag is selected from the group consisting of:

.

16. The bifunctional compound of any one of claims 1 - 8, wherein the linker is a moiety according to FORMULA 16:

FORMULA 16, wherein A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR¹, C(S)NR¹, O, S, SO, SO₂, SO₂NR¹, NR¹, NR¹CO, NR¹CONR², NR¹C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy,optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R¹ and R² are independently selected from hydrogen, optionally substituted C1- C₈ alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted 3-8 membered cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; and m is 0 to 15. 17. The bifunctional compound of any one of claims 1 - 8, wherein the linker is a moiety according to FORMULA 16A:

FORMULA 16A, wherein R¹, R², R³, and R⁴, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted C₃-C₈ cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A, W, and B, at each occurrence, are independently selected from null, CO, CO2, C(O)NR⁵, C(S)NR⁵, O, S, SO, SO₂, SO₂NR⁵, NR⁵, NR⁵CO, NR⁵CONR⁶, NR⁵C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R⁵ and R⁶ are independently selected from hydrogen, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈alkylaminoC₁-C₈alkyl; m is 0 to 15; n, at each occurrence, is 0 to 15; and o is 0 to 15. 18. The bifunctional compound of any one of claims 1 - 8, wherein the linker is a moiety according to FORMULA 16B:

FORMULA 16B, wherein ¹⁵ R¹ and R², at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C₁-C₈alkylaminoC₁-C₈alkyl; A and B, at each occurrence, are independently selected from null, CO, CO₂, C(O)NR³, C(S)NR³, O, S, SO, SO₂, SO₂NR³, NR³, NR³CO, NR³CONR⁴, NR³C(S), and optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl optionally substituted 3-8 membered cycloalkyl optionally substituted C3-C8 cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃- C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, or C₃-C₁₃ spiro heterocyclyl; wherein R³ and R⁴ are independently selected from hydrogen, and optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, or C₁-C₈alkylamino C₁-C₈alkyl; each m is 0 to 15; and n is 0 to 15. 19. The bifunctional compound of any one of claims 1 - 8, wherein the linker is a moiety according to FORMULA 16C:

FORMULA 16C, wherein X is selected from O, NH, and NR⁷; R¹, R², R³, R⁴, R⁵, and R⁶, at each occurrence, are independently selected from hydrogen, halogen, CN, OH, NH₂, optionally substituted C₁-C₈ alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; A and B, at each occurrence, are independently selected from null, CO, NH, NH-CO, CO-NH, CH₂-NH-CO, CH₂-CO-NH, NH-CO-CH₂, CO-NH-CH₂, CH₂-NH- CH₂-CO-NH, CH₂-NH-CH₂-NH-CO, -CO-NH, CO-NH- CH₂-NH-CH₂, CH₂-NH-CH₂, CO2, C(O)NR⁷, C(S)NR⁷, O, S, SO, SO₂, SO₂NR⁷, NR⁷, NR⁷CO, NR⁷CONR⁸, NR⁷C(S), optionally substituted C₁-C₈ alkyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈alkoxyC₁-C₈alkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₂-C₈ alkenyl, optionally substituted C₂-C₈ alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₃-C₁₃ fused cycloalkyl, optionally substituted C₃-C₁₃ fused heterocyclyl, optionally substituted C₃-C₁₃ bridged cycloalkyl, optionally substituted C₃-C₁₃ bridged heterocyclyl, optionally substituted C₃-C₁₃ spiro cycloalkyl, and optionally substituted C₃-C₁₃ spiro heterocyclyl; wherein R⁷ and R⁸ are independently selected from hydrogen, optionally substituted C1- C8 alkyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted C₃-C₈ cycloalkoxy, optionally substituted 3-8 membered heterocyclyl, optionally substituted C₁-C₈ alkoxy, optionally substituted C₁-C₈ alkoxyalkyl, optionally substituted C₁-C₈ haloalkyl, optionally substituted C₁-C₈ hydroxyalkyl, optionally substituted C₁-C₈ alkylamino, and optionally substituted C₁-C₈ alkylaminoC₁-C₈ alkyl; m, at each occurrence, is 0 to 15; n, at each occurrence, is 0 to 15; o is 0 to 15; and p is 0 to 15

20. The bifunctional compound of any one of claims 1 - 8, wherein the linker is selected from the group consisting of a ring selected from the group consisting of a 3 to 13 membered ring; a 3 to 13 membered fused ring; a 3 to 13 membered bridged ring; and a 3 to13 membered spiro ring. 21. The bifunctional compound of any one of claims 1 - 8, wherein the linker is a moiety according to one of FORMULAE C1, C2, C3, C4 and C5: ¹⁰ FORMULA C1,

FORMULA C2,

FORMULA C₃,

FORMULA C4 and

FORMULA C5.

22. A bifunctional compound selected from the group consisting of: NS106-033, NS106-034, NS106-035, NS106-036, NS106-037, NS106-038, NS106- 039, NS106-084, NS106-085, NS106-086, NS106-087, NS106-088, NS113-167, NS106-094, NS106-040, NS106-041, NS106-042, NS106-043, NS106-044, NS106- 045, NS106-046, NS106-047, NS106-048, NS106-049, NS113-044, NS113-045, NS113-046, NS113-047, NS113-048, NS113-049, NS113-050, NS113-051, NS113- 052, NS113-053, NS113-054, NS113-055, NS113-056, NS113-057, NS113-058, NS113-059, NS113-060 and NS113-061; and pharmaceutically acceptable salts thereof. 23. A bifunctional compound selected from the group consisting of: NS106-051, NS106-052, NS106-053, NS106-054, NS106-055, NS106-056, NS106-057, NS106-058, NS106-059, NS106-060, NS106-061, NS106-078, NS106-079, NS106-096, NS106-080, NS106-081, NS106-082, NS106-083, NS106-111, NS113-168, NS106-065, NS106-066, NS106-067, NS106-068, NS106-069, NS106-070,, NS106-071, NS106-072, NS106-073, NS106-074, NS113-093, NS106-075, NS113-094, NS106-076, NS113-095, NS113-096, NS106-077, NS113-028, NS113-029, NS113-030, NS113-031, NS113-032, NS113-033, NS113-034, NS113-083, NS113-084, NS113-085, NS113-086, NS113-087, NS113-039, NS113-040, NS113-041, NS113-042, NS113-043, NS113-088, NS113-089, NS113-090, NS113-091 and NS113-092; and pharmaceutically acceptable salts thereof.

24. A bifunctional compound selected from the group consisting of: NS113-075, NS113-076, NS113-077, NS113-078, NS113-079, NS113-080, NS113-081 and NS113-082; and pharmaceutically acceptable salts thereof. 25. A bifunctional compound selected from the group consisting of: a) N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N9-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)nonanediamide (NS106-070); b) (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((6-((6-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)amino)-6-oxohexyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-043); c) (2S,4R)-1-(2-(1-fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)- 4-hydroxy-N-((S)-3-((12-(7-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino- 5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hept-6-ynamido)dodecyl)amino)-1-(4-(4-methylthiazol-5- yl)phenyl)-3-oxopropyl)pyrrolidine-2-carboxamide (NS113-054); d) (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((2-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)ethyl)amino)-2-oxoethoxy)- 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-055); e) (2S,4R)-1-((S)-2-(1-fluorocyclopropane-1-carboxamido)-3,3- dimethylbutanoyl)-4-hydroxy-N-(2-(2-((3-(7-(3-((3-((1r,4r)-4- hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)methyl)phenyl)hept-6-ynamido)propyl)amino)-2- oxoethoxy)-4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-056); f) (2S,4R)-1-((S)-2-(tert-butyl)-21-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)-4,14-dioxo-6,9,12-trioxa-3,15-diazahenicos-20-ynoyl)-4- hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (NS113-094); and g) N1-((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-N17-(6- (3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)-3,6,9,12,15- pentaoxaheptadecanediamide (NS113-096). 26. A bifunctional compound selected from the group consisting of: a) 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(6-(3-((3- ((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4-dihydro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS106-078); and b) 3-(4-(5-((6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl-3,4- dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)amino)pent-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (NS113- 168). ²⁷ A bifunctional compound selected from the group consisting of: a) (3r,5r,7r)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4-imino-5,6-diphenyl- 3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)phenyl)hex-5-yn-1- yl)adamantane-1-carboxamide (NS121-135); and b) 2-((3r,5r,7r)-adamantan-1-yl)-N-(6-(3-((3-((1r,4r)-4-hydroxycyclohexyl)-4- imino-5,6-diphenyl-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7- yl)methyl)phenyl)hex-5-yn-1-yl)acetamide (NS121-136). 28. A method of treating a subject having an eFF1A2-mediated disease, the method comprising administering to a subject in need thereof, a bifunctional compound according to one of claims 1 – 27. 29. The method of claim 28, wherein the eEF1A2-mediated disease is selected from the group consisting of solid and liquid cancers, chronic infections that produce exhausted immune response, infection-mediated immune suppression, age-related decline in immune response, age-related decline in cognitive function and infertility. 30. A method of decreasing the level of eFF1A2 in a subject in need thereof, the method comprising administering to a subject in need thereof, a bifunctional compound according to one of claims 1 – 27. 31. The method according to one of claims 28 – 20, wherein the bifunctional compound is administered orally, parenterally, intradermally, subcutaneously, topically, and/or rectally. 32. A pharmaceutical composition, comprising a bifunctional compound according to one of claims 1 – 27 and a pharmaceutically acceptable carrier.

33. A method of treating a subject having a perinucleolar compartment metastatic protein-mediated disease, the method comprising administering to a subject in need thereof, a bifunctional compound according to one of claims 1 – 27. 34. The method according to claim 29, wherein the cancer is a metastatic solid tumor selected from the group consisting of advanced solid tumors, metastatic pancreatic cancer, pediatric solid tumor, advanced breast cancer, malignant peripheral nerve sheath tumor and colorectal neoplasms.