WO2023040981A1

WO2023040981A1 - Methods and compositions for weight management

Info

Publication number: WO2023040981A1
Application number: PCT/CN2022/119093
Authority: WO
Inventors: Ng Meng HUA; Ruiqi Rachel WANG; Kun Liang; Zipeng ZHENG; Jie Yang
Original assignee: Aegogen (Suzhou) Limited
Priority date: 2021-09-20
Filing date: 2022-09-15
Publication date: 2023-03-23
Also published as: CN118215474A

Abstract

This present application relates to the use of small molecules for weight management, prevention of aging and the treatment of associated conditions and diseases. The present application also provides for the synthesis of some of the molecules and the administration of these molecules for drug discovery, nutrition and cosmeceutical purposes.

Description

METHODS AND COMPOSITIONS FOR WEIGHT MANAGEMENT

FIELD

This present relates to the use of small molecules for weight management

BACKGROUND

Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Given the proportion of the world’s population aged >60 years doubles over the next four decades, the increased incidences of chronic age-related diseases will place a huge burden on healthcare resources.

Across populations today, muscle mass and weight remains relatively stable during early life, but after age ～50 years, muscle mass declines at a rate of ～1%per year. With aging, the impaired balance between protein synthesis and proteolysis in skeletal muscle results in a progressive decline in body weight, uncontrolled involuntary weight loss, skeletal muscle mass, strength and function, and is defined as sarcopenia. As the strength of limb muscles and respiratory muscles gradually decrease, physical functions and activities such as breathing, standing, walking and running will also decline. On average, the peak strength decreases by 20-40%between 20-30 and 70-80 years old. Loss of muscle and massive loss of body weight has a serious consequence on many chronic diseases, and on aging itself, because it leads to weakness, loss of independence, and increased risk of death. Various myokines released from active muscles act as signaling mediators between skeletal muscle and other vital organs, such as the liver, fat and brain. This signaling influences the progression of chronic disease such as diabetes, cardiovascular disease, osteoporosis, osteoarthritis, cancer, and many other aging-related diseases. Thus, sarcopenia represents a major health problem and an important burden for healthcare systems across the globe. Beyond sarcopenia, uncontrolled involuntary weight loss also occurs in the context of many chronic diseases, such as cancer, chronic obstructive pulmonary disease (COPD) , chronic kidney disease (CKD) etc, in a phenomenon known as cachexia.

BRIEF SUMMARY

This application provides compositions and methods of using small molecules or naturally occurring substances for weight management.

One aspect of this application provides a composition of matter for weight management, comprising compound B, or a salt, solvate, tautomer, analog or stereoisomer thereof. One aspect of this application provides a composition for inducing increase of muscle and fat mass, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof.

One aspect of this application, provides a composition of matter to replenish nutrition to help increase muscle and fat mass, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof.

One aspect of this application, provides a composition of matter to prevent or treat uncontrolled involuntary weight loss, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof.

One aspect of this application provides a composition of matter to enable weight restoration in uncontrolled involuntary weight loss, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof.

One aspect of this application provides a composition of matter to enable growth of muscle and fat in uncontrolled involuntary weight loss, comprising one or compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof.

In some embodiments the compositions of matter are administered to an aged individual, e.g., a human individual of at least about any one of 50, 60, 70, 80, or more years old. One aspect of this application provides a method of treating a disease or condition in an individual, comprising administering an effective amount of a composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof to the individual. In some embodiments, the composition is administered to the tissue of the individual. In some embodiments, possible routes of administration include but is not limited to: oral, sublingual, buccal, nasal, inhalation, intratracheal, intravenous, intraarterial, intracoronary, intrathecal, intramuscular, intraperitoneal, intramyocardial, trans-endocardial, trans-epicardial, subcutaneous, transdermal, vaginal, rectal, or otic.

In some embodiments according to any one of the methods of treatment described above, the disease or condition is tissue degeneration.

In some embodiments according to any one of the methods of treatment described above, the disease or condition is aging.

In some embodiments according to any one of the compositions of matter described above, the disease or condition is selected from the group consisting of sarcopenia, and cachexia, tissue atrophy and disuse atrophy.

These and other aspects and advantages of the present invention will become apparent from the subsequent detailed description and the appended claims. It is to be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the schematic for modeling inflammaging in vivo, by using bleomycin (3mg/kg in 50ul PBS, intratracheal) to induce chronic obstructive pulmonary disease (COPD) , cytokine release syndrome (CRS) , sarcopenia and cachexia.

FIG. 2 shows the quantification of the Kaplan-Meier survival curves for inflammaging mice.

FIG. 3 shows the total body weight (%of initial weight) changes for inflammaging mice.

FIG. 4 shows the limb tissue mass (grams) for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly prevented loss of tissue mass and promoted tissuegenesis, tissue growth and tissue repair, compared to leucine (L) alone, or DMSO vehicle treatment.

FIG. 5 shows the serum lactate dehydrogenase (LDH) levels for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29 significantly reduced cellular damage, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment.

FIG. 6 shows the quantification of new Myh3+ myofibers that incorporated muscle stem cells (BrdU+) (**P<0.01) .

FIG. 7 shows weight change upon addition of DMSO vehicle control, 22, leucine and 22 with two different amounts of leucine respectively to cachexia mouse models induced by bleomycin. The results show that 22+leucine (low) restores weight in cachexia mice faster and to a greater extent compared to DMSO vehicle control, 22 only, leucine only, or 22+leucine (high) .

FIG. 8 shows that change in muscle cell proliferation upon addition of DMSO vehicle control (control) , 22, leucine (leu) and 22 + leucine (22+leu) respectively to cachexia mouse models induced by bleomycin. A shows the immunostaining for ki67 (proliferation marker) and Pax7 (muscle cell marker) and B shows the quantification results of the aforementioned immunostaining results.

FIG. 9 shows that changes in (A) cross sectional area (CSA) and (B) Feret Diameter of mouse myofibers upon addition of DMSO vehicle control (control) , 22, leucine and 22 + leucine (22+leu) respectively to cachexia mouse models induced by bleomycin.

FIG. 10 shows western blot analysis of mouse muscles upon addition of DMSO vehicle control (control) , 22, leucine (leu) and 22 + leucine (22+leu) respectively to cachexia mouse models induced by bleomycin, where combination of 22 and leucine increases phospho-S6 and MHC, in comparison with 22, leucine alone or DMSO controls.

FIG. 11 shows the lung tissue sections of both treated and untreated cachexia mouse models, with Masson Trichome staining, where blue represents fibrosis. FIG 11A shows the lung section stained the untreated cachexia mouse model, whereas FIG 11B shows the lung section of the cachexia mouse model treated with 22+L with Mason Trichome staining. FIG 11C shows the blue channel of FIG 11A extracted with ImageJ for further quantification and FIG 11D shows the blue channel of FIG 11B extracted with ImageJ for further quantification. FIG 11E shows the quantification results of FIG 11C and FIG 11D that have been normalized against for the given area of the respective tissue sections.

FIG. 12 shows hematoxylin and eosin (H&E) staining of the lung sections of the vehicle control-treated mice (untreated) and mice treated with 20mg/kg of 22 and 10ng/kg of leucine (treated) .

FIG. 13 shows forelimb grip strength of vehicle control-treated mice (untreated) and mice treated with 20mg/kg of 22 and 10mg/kg of leucine (treated) .

FIG. 14 shows clinical hematology of cachexia mice models induced by bleomycin treated with DMSO vehicle control (Control) and 22+leucine (Treated) in comparison with clinical hematology of normal healthy mice (Normal Mice) . As shown here, treatment with 22+leucine decreases inflammatory Neutrophils (Neu) , restores white blood cells (WBC) , lymphocytes (Lym) , monocytes (Mono) to higher normal levels and restores red blood cells to normal lower levels.

FIG. 15 shows platelet counts of cachexia mice models treated with DMSO vehicle control (Control) and 22+L (Treated) in comparison with platelets counts of normal healthy mice (Normal Mice) .

FIG. 16 shows uric acid levels of control mice (treated with DMSO) and mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) and 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) . Uric acid (UA) , the end-product of the purine metabolism, is elevated in cachexia due to tissue wasting and upregulated xanthine oxidase (XO) activity.

FIG. 17 shows creatinine levels of control mice (treated with DMSO) and mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) and 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) .

FIG. 18 shows LDL levels of control mice (treated with DMSO) and mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) and 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) .

FIG. 19 shows thigh circumferences of mice that have undergone denervation, with the sham group as control. Our results showed that the thigh circumference of the sham group was generally stable after surgery, whereas the thigh circumference of the denervation group declined steadily within 20 days after surgery. When 22+L was injected subcutaneously daily, it had little effect on the sham group, but induced a remarkable recovery in the thigh circumference of the denervated group between day 14 and day 24.

FIG. 20 shows the difference in thigh circumferences of mice treated with 22+L versus the control group where the respective sham groups are deducted from the denervation groups in FIG. 16. More detailed descriptions can be found in Example 4

FIG. 21 shows the hanging time of the mice, as a surrogate measure of the mouse strength and endurance, we found that 22+L injection (22+L) dramatically increased mouse strength and endurance, relative to PBS vehicle control injection (control) .

FIG. 22 shows the ALT levels and AST levels in cirrhosis mouse models. the control mice (control) plasma had dramatically higher levels of the liver cirrhosis markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the normal mice (normal) , whereas the treated mice (treated) had significantly lower levels of the liver cirrhosis markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver cirrhosis.

FIG. 23 shows direct bilirubin (DBIL) and total bilirubin (TBIL) in cirrhosis mouse models. The control mice (control) plasma had higher levels of the biliary cirrhosis markers direct bilirubin (DBIL) and total bilirubin (TBIL) than the normal mouse (normal) , whereas the treated mice (treated) had significantly lower levels of the biliary cirrhosis markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver biliary cirrhosis.

FIG 24. shows liver biosynthetic function markers in cirrhosis mouse models. the control mice (control) plasma had dramatically lower levels of the liver biosynthetic function markers cholesterol (CHOL) , HDLc (high density lipoprotein cholesterol) and LDLc (low density lipoprotein cholesterol) , than the normal mouse (normal) , as is indicative of cirrhotic hypocholesterolemia and chronic hepatic insufficiency (see DOI: 10.1080/00365529850172593) , whereas the treated mice (treated) had significantly higher and near-normal levels of these liver biosynthetic function markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver cirrhosis.

DETAILED DESCRIPTION

The present application provides compositions and methods for administrating wherein the composition and methods of comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof for weight management. In some embodiments, the composition comprises of both compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof and amino acids and/or peptides. The present application is at least in part based on the inventors’ surprising discovery of the usage of a composition of small molecules to boost regeneration and growth of tissue in vitro and in vivo. The methods and compositions described herein can be used for weight management, muscle, fat and weight gain and restoration in conditions associated with uncontrolled involuntary weight and muscle loss.

I. Definitions

Terms are used herein as generally used in the art, unless otherwise defined as follows. As used herein, “regeneration” refers to the process of replacing or restoring damaged or missing cells, tissues, organs, and even entire body parts to full function in plants and animals.

As used herein, “rejuvenation” refers to the process of restoring damaged or old cells, tissues, organs and even entire body parts to a healthy or young state.

As used herein, “tissuegenesis” refers to the process of tissue formation.

As used herein, “treat” , "treatment" or "treating" is an approach for obtaining beneficial or desired results including clinical results. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, one or more of the following: decreasing one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease or condition (e.g., reversing or delaying the worsening of the disease or condition) , reversing or delaying the spread of the disease or condition, reversing or delaying the occurrence or recurrence of the disease or condition, delaying or reversing the progression of the disease or condition, ameliorating the disease state, providing a remission (whether partial or total) of the disease or condition, decreasing the dose of one or more other medications required to treat the disease or condition, delaying the progression of the disease or condition, increasing the quality of life, and/or prolonging survival. Also encompassed by "treatment" is a reduction of pathological consequence of the disease or condition. The methods of the present application contemplate any one or more of these aspects of treatment.

As used herein, “reverse” or “reversal” to the process of making something the opposite of what it is to restore the cell, tissue, organ or part of the whole body to its optimal health or function.

The terms “individual, ” “subject” and “patient” are used interchangeably herein to describe a mammal, including humans. An individual includes, but is not limited to, human, bovine, ovine, porcine, equine, feline, canine, rodent, or primate. In some embodiments, the individual is human. In some embodiments, an individual suffers from a disease or condition. In some embodiments, the individual is in need of treatment. In some embodiments, the individual is an aged individual, e.g., a human individual of at least about any one of 50, 55, 60, 65, 70, 75, 80, 85 or more years old.

As is understood in the art, an “effective amount” refers to an amount of a composition sufficient to produce a desired therapeutic outcome. For therapeutic use, beneficial or desired results include, e.g., decreasing one or more symptoms resulting from the disease or condition (biochemical, histologic and/or behavioral) , including its complications and intermediate pathological phenotypes presented during development of the disease or condition, increasing the quality of life of those suffering from the disease or condition, decreasing the dose of other medications required to treat the disease or condition, enhancing effect of another medication, delaying the progression of the disease or condition, and/or prolonging survival of patients.

As used herein, the terms “cell” and “cell culture” are used interchangeably and all such designations include progeny. It is understood that all progeny may not be precisely identical in DNA content, due to deliberate or inadvertent mutations. Variant progeny that has the same function or biological activity as the original cells are included.

“Alkyl” refers to monovalent saturated aliphatic hydrocarbyl groups having from 1 to 10 carbon atoms and preferably 1 to 6 carbon atoms. This term includes, by way of example, linear and branched hydrocarbyl groups such as methyl (CH ₃-) , ethyl (CH ₃CH ₂-) , n-propyl (CH ₃CH ₂CH ₂-) , isopropyl ( (CH ₃) ₂CH-) , n-butyl (CH ₃CH ₂CH ₂CH ₂-) , isobutyl ( (CH ₃) ₂CHCH ₂-) , sec-butyl ( (CH ₃) (CH ₃CH ₂) CH-) , t-butyl ( (CH ₃) ₃C-) , n-pentyl (CH ₃CH ₂CH ₂CH ₂CH ₂-) , neopentyl ( (CH ₃) ₃CCH ₂-) , and n-hexyl (CH ₃ (CH ₂) ₅-) .

“Alkylene” refers to divalent aliphatic hydrocarbylene groups preferably having from 1 to 10 and more preferably 1 to 3 carbon atoms that are either straight-chained or branched. This term includes, by way of example, methylene (-CH ₂-) , ethylene (-CH ₂CH ₂-) , n-propylene (-CH ₂CH ₂CH ₂-) , iso-propylene (-CH ₂CH (CH ₃) -) , (-C (CH ₃) ₂CH ₂CH ₂-) , (-C (CH ₃) ₂CH ₂C (O) -) , (-C (CH ₃) ₂CH ₂C (O) NH-) , (-CH (CH ₃) CH ₂-) , and the like.

“Alkenyl” refers to straight chain or branched hydrocarbyl groups having from 2 to 10 carbon atoms and preferably 2 to 4 carbon atoms and having at least 1 and preferably from 1 to 2 sites of double bond unsaturation. This term includes, by way of example, bi-vinyl, allyl, and but-3-en-1-yl. Included within this term are the cis and trans isomers or mixtures of these isomers.

“Alkenylene” refers to straight chain or branched hydrocarbylene groups having from 2 to 10 carbon atoms and preferably 2 to 4 carbon atoms and having at least 1 and preferably from 1 to 2 sites of double bond unsaturation. Examples of alkenylene include, but is not limited to, vinylene (-CH=CH-) , allylene (-CH ₂C=C-) , and but-3-en-1-ylene (-CH ₂CH ₂C=CH-) . Included within this term are the cis and trans isomers or mixtures of these isomers.

“Alkynyl” refers to straight or branched hydrocarbyl groups having from 2 to 6 carbon atoms and preferably 2 to 3 carbon atoms and having at least 1 and preferably from 1 to 2 sites of triple bond unsaturation. Examples of such alkynyl groups include acetylenyl (-C≡CH) , and propargyl (-CH ₂C≡CH) .

“Alkynylene” refers to straight or branched hydrocarbylene groups having from 2 to 6 carbon atoms and preferably 2 to 3 carbon atoms and having at least 1 and preferably from 1 to 2 sites of triple bond unsaturation. Examples of alkynylene include, but are not limited to, acetylenylene (-C≡C-) , and propargylene (-CH ₂C≡C-) .

“Amino” refers to the group -NH ₂.

“Substituted amino” refers to the group -NRR where each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl, and heterocyclyl provided that at least one R is not hydrogen.

“Aryl” refers to a monovalent aromatic carbocyclic group of from 6 to 18 carbon atoms having a single ring (such as is present in a phenyl group) or a ring system having multiple condensed rings (examples of such aromatic ring systems include naphthyl, anthryl and indanyl) which condensed rings may or may not be aromatic, provided that the point of attachment is through an atom of an aromatic ring. This term includes, by way of example, phenyl and naphthyl. Unless otherwise constrained by the definition for the aryl substituent, such aryl groups can optionally be substituted with from 1 to 5 substituents, or from 1 to 3 substituents, selected from acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxyl ester, cyano, halogen, nitro, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, sulfonylamino, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂-alkyl, -SO ₂-substituted alkyl, -SO ₂-aryl, -SO ₂-heteroaryl and trihalomethyl.

“Cycloalkyl” refers to cyclic alkyl groups of from 3 to 10 carbon atoms having single or multiple cyclic rings including fused, bridged, and spiro ring systems. Examples of suitable cycloalkyl groups include, for instance, adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl and the like. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like, or multiple ring structures such as adamantyl, and the like.

“Heteroaryl” refers to an aromatic group of from 1 to 15 carbon atoms, such as from 1 to 10 carbon atoms and 1 to 10 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur within the ring. Such heteroaryl groups can have a single ring (such as, pyridinyl, imidazolyl or furyl) or multiple condensed rings in a ring system (for example as in groups such as, indolizinyl, quinolinyl, benzofuranyl, benzimidazolyl or benzothienyl) , wherein at least one ring within the ring system is aromatic and at least one ring within the ring system is aromatic, provided that the point of attachment is through an atom of an aromatic ring. In certain embodiments, the nitrogen and/or sulfur ring atom (s) of the heteroaryl group are optionally oxidized to provide for the N-oxide (N→O) , sulfinyl, or sulfonyl moieties. This term includes, by way of example, pyridinyl, pyrrolyl, indolyl, thiophenyl, and furanyl. Unless otherwise constrained by the definition for the heteroaryl substituent, such heteroaryl groups can be optionally substituted with 1 to 5 substituents, or from 1 to 3 substituents, selected from acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxyl ester, cyano, halogen, nitro, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, sulfonylamino, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO ₂-alkyl, -SO ₂-substituted alkyl, -SO ₂-aryl and -SO ₂-heteroaryl, and trihalomethyl.

Examples of heteroaryls include, but are not limited to, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, purine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, piperidine, piperazine, phthalimide, 4, 5, 6, 7-tetrahydrobenzo [b] thiophene, thiazole, thiophene, benzo [b] thiophene, and the like.

“Heterocycle, ” “heterocyclic, ” “heterocycloalkyl” or “heterocyclyl” refers to a saturated or partially unsaturated group having a single ring or multiple condensed rings, including fused, bridged, or spiro ring systems, and having from 3 to 20 ring atoms, including 1 to 10 hetero atoms. These ring atoms are selected from the group consisting of carbon, nitrogen, sulfur, or oxygen, wherein, in fused ring systems, one or more of the rings can be cycloalkyl, aryl, or heteroaryl, provided that the point of attachment is through the non-aromatic ring. In certain embodiments, the nitrogen and/or sulfur atom (s) of the heterocyclic group are optionally oxidized to provide for N-oxide, -S (O) -, or-SO ₂-moieties.

Examples of heterocycles include, but are not limited to, azetidine, dihydroindole, indazole, quinolizine, imidazolidine, imidazoline, piperidine, piperazine, indoline, 1, 2, 3, 4-tetrahydroisoquinoline, thiazolidine, morpholinyl, thiomorpholinyl (also referred to as thiamorpholinyl) , 1, 1-dioxothiomorpholinyl, piperidinyl, pyrrolidine, tetrahydrofuranyl, and the like.

Where a heteroaryl or heterocyclyl group is “substituted, ” unless otherwise constrained by the definition for the heteroaryl or heterocyclic substituent, such heteroaryl or heterocyclic groups can be substituted with 1 to 5, or from 1 to 3 substituents, selected from alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, azido, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carboxyl ester, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, sulfonylamino, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO-heterocyclyl, -SO ₂-alkyl, -SO ₂-substituted alkyl, -SO ₂-aryl, ―SO ₂―heteroaryl, and -SO ₂-heterocyclyl.

“Polyalkylene glycol” refers to straight or branched polyalkylene glycol polymers such as polyethylene glycol, polypropylene glycol, and polybutylene glycol. A polyalkylene glycol subunit is a single polyalkylene glycol unit. For example, an example of a polyethylene glycol subunit would be an ethylene glycol, -O-CH ₂-CH ₂-O-, or propylene glycol, -O-CH ₂-CH ₂-CH ₂-O-capped with a hydrogen at the chain termination point. Other examples of poly (alkylene glycol) include, but are not limited to, PEG, PEG derivatives such as methoxypoly (ethylene glycol) (mPEG) , poly (ethylene oxide) , PPG, poly (tetramethylene glycol) , poly (ethylene oxide-co-propylene oxide) , or copolymers and combinations thereof.

“Polyamine” refers to polymers having an amine functionality in the monomer unit, either incorporated into the backbone, as in polyalkyleneimines, or in a pendant group as in polyvinyl amines.

In addition to the application herein, the term “substituted, ” when used to modify a specified group or radical, can also mean that one or more hydrogen atoms of the specified group or radical are each, independently of one another, replaced with the same or different substituent groups as defined below.

In addition to the groups disclosed with respect to the individual terms herein, substituent groups for substituting for one or more hydrogens (any two hydrogens on a single carbon can be replaced with =O, =NR ⁷⁰, =N-OR ⁷⁰, =N ₂ or =S) on saturated carbon atoms in the specified group or radical are, unless otherwise specified, -R ⁶⁰, halo, =O, -OR ⁷⁰, -SR ⁷⁰, -NR ⁸⁰R ⁸⁰, trihalomethyl, -CN, -OCN, -SCN, -NO, -NO ₂, =N ₂, -N ₃, -S (O) R ⁷⁰, -S (O) ₂R ⁷⁰, -SO ₃ ^–M ⁺, -S (O) ₂OR ⁷⁰, -OS (O) ₂R ⁷⁰, -OSO ₃ ^–M ⁺, -OS (O) ₂OR ⁷⁰, -PO ₃ ^2– (M ⁺) ₂, -P (O) (OR ⁷⁰) O ^–M ⁺, -P (O) (OR ⁷⁰) ₂, -C (O) R ⁷⁰, -C (S) R ⁷⁰, -C (NR ⁷⁰) R ⁷⁰, -C (O) O ^–M ⁺, -C (O) OR ⁷⁰, -C (S) OR ⁷⁰, -C (O) NR ⁸⁰R ⁸⁰, -C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, -OC (O) R ⁷⁰, -OC (S) R ⁷⁰, -OC (O) O ^-M ⁺, -OC (O) OR ⁷⁰, -OC (S) OR ⁷⁰, -NR ⁷⁰C (O) R ⁷⁰, -NR ⁷⁰C (S) R ⁷⁰, -NR ⁷⁰CO ₂ ^–M ⁺, -NR ⁷⁰CO ₂R ⁷⁰, -NR ⁷⁰C (S) OR ⁷⁰, -NR ⁷⁰C (O) NR ⁸⁰R ⁸⁰, -NR ⁷⁰C (NR ⁷⁰) R ⁷⁰ and -NR ⁷⁰C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, where R ⁶⁰ is selected from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, each R ⁷⁰ is independently hydrogen or R ⁶⁰; each R ⁸⁰ is independently R ⁷⁰ or alternatively, two R ⁸⁰'s, taken together with the nitrogen atom to which they are bonded, form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl which may optionally include from 1 to 4 of the same or different additional heteroatoms selected from the group consisting of O, N and S, of which N may have –H, C ₁-C ₄ alkyl, _-C (O) C _1-4alkyl, _-CO ₂C _1-4alkyl, or -S (O) ₂C _1-4alkyl substitution; and each M ⁺ is a counter ion with a net single positive charge. Each M ⁺may independently be, for example, an alkali ion, such as K ⁺, Na ⁺, Li ⁺; an ammonium ion, such as ⁺N (R ⁶⁰) ₄; or an alkaline earth ion, such as [Ca ²⁺] _0.5, [Mg ²⁺] _0.5, or [Ba ²⁺] _0.5 ( "subscript 0.5 means that one of the counter ions for such divalent alkali earth ions can be an ionized form of a compound of the embodiments and the other a typical counter ion such as chloride, or two ionized compounds disclosed herein can serve as counter ions for such divalent alkali earth ions, or a doubly ionized compound of the embodiments can serve as the counter ion for such divalent alkali earth ions) .

In addition to the application herein, substituent groups for hydrogens on unsaturated carbon atoms in "substituted" alkene, alkyne, aryl and heteroaryl groups are, unless otherwise specified, -R ⁶⁰, halo, -O ^–M ⁺, -OR ⁷⁰, -SR ⁷⁰, -S ^–M ⁺, -NR ⁸⁰R ⁸⁰, trihalomethyl, -CF ₃, -CN, -OCN, -SCN, -NO, -NO ₂, -N ₃, -S (O) R ⁷⁰, -S (O) ₂R ⁷⁰, -SO ₃ ^–M ⁺, -SO ₃R ⁷⁰, -OS (O) ₂R ⁷⁰, -OSO ₃ ^–M ⁺, -OSO ₃R ⁷⁰, -PO ₃ ^2– (M ⁺) ₂, -P (O) (OR ⁷⁰) O ^–M ⁺, -P (O) (OR ⁷⁰) ₂, -C (O) R ⁷⁰, -C (S) R ⁷⁰, -C (NR ⁷⁰) R ⁷⁰, -CO ₂ ^–M ⁺, -CO ₂R ⁷⁰, -C (S) OR ⁷⁰, -C (O) NR ⁸⁰R ⁸⁰, -C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, -OC (O) R ⁷⁰, -OC (S) R ⁷⁰, -OCO ₂ ^–M ⁺, -OCO ₂R ⁷⁰, -OC (S) OR ⁷⁰, -NR ⁷⁰C (O) R ⁷⁰, -NR ⁷⁰C (S) R ⁷⁰, -NR ⁷⁰CO ₂ ^–M ⁺, -NR ⁷⁰CO ₂R ⁷⁰, -NR ⁷⁰C (S) OR ⁷⁰, -NR ⁷⁰C (O) NR ⁸⁰R ⁸⁰, -NR ⁷⁰C (NR ⁷⁰) R ⁷⁰ and -NR ⁷⁰C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, where R ⁶⁰, R ⁷⁰, R ⁸⁰ and M ⁺ are as previously defined, provided that in case of substituted alkene or alkyne, the substituents are not -O ^–M ⁺, -OR ⁷⁰, -SR ⁷⁰, or -S ^–M ⁺.

In addition to the substituent groups disclosed with respect to the individual terms herein, substituent groups for hydrogens on nitrogen atoms in “substituted” heterocycloalkyl and cycloalkyl groups are, unless otherwise specified, -R ⁶⁰, -O ^–M ⁺, -OR ⁷⁰, -SR ⁷⁰, -S ^–M ⁺, -NR ⁸⁰R ⁸⁰, trihalomethyl, -CF ₃, -CN, -NO, -NO ₂, -S (O) R ⁷⁰, -S (O) ₂R ⁷⁰, -S (O) ₂O ^–M ⁺, -S (O) ₂OR ⁷⁰, -OS (O) ₂R ⁷⁰, -OS (O) ₂O ^–M ⁺, -OS (O) ₂OR ⁷⁰, -PO ₃ ^2– (M ⁺) ₂, -P (O) (OR ⁷⁰) O ^–M ⁺, -P (O) (OR ⁷⁰) (OR ⁷⁰) , -C (O) R ⁷⁰, -C (S) R ⁷⁰, -C (NR ⁷⁰) R ⁷⁰, -C (O) OR ⁷⁰, -C (S) OR ⁷⁰, -C (O) NR ⁸⁰R ⁸⁰, -C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, -OC (O) R ⁷⁰, -OC (S) R ⁷⁰, -OC (O) OR ⁷⁰, -OC (S) OR ⁷⁰, -NR ⁷⁰C (O) R ⁷⁰, -NR ⁷⁰C (S) R ⁷⁰, -NR ⁷⁰C (O) OR ⁷⁰, -NR ⁷⁰C (S) OR ⁷⁰, -NR ⁷⁰C (O) NR ⁸⁰R ⁸⁰, -NR ⁷⁰C (NR ⁷⁰) R ⁷⁰ and -NR ⁷⁰C (NR ⁷⁰) NR ⁸⁰R ⁸⁰, where R ⁶⁰, R ⁷⁰, R ⁸⁰ and M ⁺ are as previously defined.

In addition to the application herein, in a certain embodiment, a group that is substituted has 1, 2, 3, or 4 substituents, 1, 2, or 3 substituents, 1 or 2 substituents, or 1 substituent. It is understood that in all substituted groups defined above, polymers arrived at by defining substituents with further substituents to themselves (e.g., substituted aryl having a substituted aryl group as a substituent which is itself substituted with a substituted aryl group, which is further substituted by a substituted aryl group, etc. ) are not intended for inclusion herein. In such cases, the maximum number of such substitutions is three. For example, serial substitutions of substituted aryl groups specifically contemplated herein are limited to substituted aryl- (substituted aryl) -substituted aryl.

Unless indicated otherwise, the nomenclature of substituents that are not explicitly defined herein are arrived at by naming the terminal portion of the functionality followed by the adjacent functionality toward the point of attachment. For example, the substituent “arylalkyloxycarbonyl” refers to the group (aryl) - (alkyl) -O-C (O) -.

As to any of the groups disclosed herein which contain one or more substituents, it is understood, of course, that such groups do not contain any substitution or substitution patterns which are sterically impractical and/or synthetically non-feasible. In addition, the subject compounds include all stereochemical isomers arising from the substitution of these compounds.

The term “pharmaceutically acceptable salt” means a salt which is acceptable for administration to a patient, such as a mammal (salts with counterions having acceptable mammalian safety for a given dosage regime) . Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids. “Pharmaceutically acceptable salt” refers to pharmaceutically acceptable salts of a compound, which salts are derived from a variety of organic and inorganic counter ions well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, formate, tartrate, besylate, mesylate, acetate, maleate, oxalate, and the like.

The term “salt thereof” means a compound formed when a proton of an acid is replaced by a cation, such as a metal cation or an organic cation and the like. Where applicable, the salt is a pharmaceutically acceptable salt, although this is not required for salts of intermediate compounds that are not intended for administration to a patient. By way of example, salts of the present compounds include those wherein the compound is protonated by an inorganic or organic acid to form a cation, with the conjugate base of the inorganic or organic acid as the anionic component of the salt.

“Solvate” refers to a complex formed by combination of solvent molecules with molecules or ions of the solute. The solvent can be an organic compound, an inorganic compound, or a mixture of both. Some examples of solvents include, but are not limited to, methanol, N, N-dimethylformamide, tetrahydrofuran, dimethylsulfoxide, and water. When the solvent is water, the solvate formed is a hydrate.

“Stereoisomer” and “stereoisomers” refer to compounds that have same atomic connectivity but different atomic arrangement in space. Stereoisomers include cis-trans isomers, E and Z isomers, enantiomers, and diastereomers.

“Tautomer” refers to alternate forms of a molecule that differ only in electronic bonding of atoms and/or in the position of a proton, such as enol-keto and imine-enamine tautomers, or the tautomeric forms of heteroaryl groups containing a -N=C (H) -NH-ring atom arrangement, such as pyrazoles, imidazoles, benzimidazoles, triazoles, and tetrazoles. A person of ordinary skill in the art would recognize that other tautomeric ring atom arrangements are possible.

It will be appreciated that the term "or a salt or solvate or tautomer or stereoisomer thereof" is intended to include all permutations of salts, solvates, tautomers, and stereoisomers, such as a solvate of a pharmaceutically acceptable salt of a tautomer of a stereoisomer of subject compound.

It is understood that aspect and embodiments of the invention described herein include “consisting” and/or “consisting essentially of” aspects and embodiments.

Reference to "about" a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to "about X" includes description of "X" .

The term “about X-Y” used herein has the same meaning as “about X to about Y. ”

As used herein, reference to "not" a value or parameter generally means and describes "other than" a value or parameter. For example, the method is not used to treat cancer of type X means the method is used to treat cancer of types other than X.

As used herein and in the appended claims, the singular forms "a, " "an, " and "the" include plural referents unless the context clearly dictates otherwise.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

II. Composition of matter to promote tissue regeneration

The present application provides composition of matter for weight management using compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the composition for weight management comprises of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the said composition of matter provides replenishment of nutrition for weight management. The methods described herein can promote tissue regeneration both after injury and without injury (i.e., woundless tissue regeneration) . In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to promote weight gain in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, there is provided a composition of matter to promote weight gain in an individual, the composition comprises of both compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter for promoting muscle or limb mass gain in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the said composition of matter provides replenishment of nutrition for promoting muscle or limb mass gain in an individual. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, there is provided a composition of matter for promoting weight gain in an individual, the composition comprises of both compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to treat and/or prevent involuntary weight loss, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the said composition of matter replenishes nutrition to treat and/or prevent involuntary weight loss in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, the weight loss is uncontrolled. In some embodiments, there is provided a composition of matter to treat and/or prevent involuntary weight loss, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, the weight loss is uncontrolled. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to enable weight restoration in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the said composition of matter replenishes nutrition to enable weight restoration in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the individual is an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, the weight loss is uncontrolled. In some embodiments, there is provided a composition of matter to enable weight restoration in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual has undergone injury or disease. In some embodiments, the individual has not undergone any injury or diseases. In some embodiments, the weight loss is uncontrolled. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to promote physical endurance in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the said composition of matter replenishes nutrition to promote physical endurance in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the individual is an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the individual is an injured individual. In some embodiments, the individual has not undergone injury. In some embodiments, there is provided a composition of matter for promoting physical endurance in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, there is provided a composition of matter to replenish nutrition promote physical endurance in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual is an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the individual is an injured individual. In some embodiments, the individual has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to relieve sports fatigue in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, there is provided a composition of matter to replenish nutrition to relieve sports fatigue in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the individual is an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the individual is an injured individual. In some embodiments, the individual has not undergone injury. In some embodiments, there is provided a composition of matter to relieve sports fatigue in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, there is provided a composition of matter to replenish nutrition to relieve sports fatigue in an individual, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the individual is an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the individual is an injured individual. In some embodiments, the individual has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to replenish nutrition and promote tissue health, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to replenish nutrition and promote tissue health, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to promote growth or repair of a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to promote growth or repair of a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to increase expression of proliferation biomarkers (e.g. ki67) within a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to increase expression of proliferation biomarkers (e.g. ki67) within a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to promote tissuegenesis, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to promote tissuegenesis, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to induce differentiation and/or maturation of a tissuegenic cell (e.g. muscle cells within a muscle) , compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to induce differentiation and/or maturation of a tissuegenic cell (e.g. muscle cells within a muscle) , compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to induce proliferation of stem cells or tissuegenic cells within a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 50 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to induce proliferation of stem cells or tissuegenic cells within a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 50 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to induce increase in tissue mass, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 50 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to induce increase in tissue mass, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 50 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to treat or reverse fibrosis, comprising of comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is a lung tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to treat or reverse fibrosis, comprising of comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to treat or reverse senescence, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is muscle. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to treat or reverse senescence, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is muscle. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a composition of matter to treat or reverse inflammaging, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, there is provided a composition of matter to treat or reverse inflammaging, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. In some embodiments, the said composition of matter provides replenishment of nutrition to reverse inflammaging. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair follicle, epithelial, urogenital, cervix, uterine, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the tissue is fat tissue. In some embodiments, the tissue is from an aged individual (e.g., a human individual of at least about 40 years old) . In some embodiments, the tissue is an injured tissue. In some embodiments, the tissue has not undergone injury. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

Tissue regeneration or rejuvenation, tissue growth, differentiation and maturation of tissuegenic cells, tissuegenesis increased expression of proliferation biomarkers, proliferation of stem cells and tissuegenic cells, differentiation and maturation of tissuegenic cells, reversal, ion or treatment of fibrosis or senescence or inflammaging, may be assessed using known methods in the art such as but not limited to microscopy, fluorescence microscopy, fluorescence in-situ hybridization, immunofluorescence, immunostaining, western blots, mass spectrometry, proteomics, transcriptomics and genomic sequencing. Protein expression levels may be determined by immunostaining or by Western blots. mRNA expression levels may be determined by quantitative reverse-transcription PCR, microarray, or next-generation sequencing.

The methods described herein are applicable to tissues and tissuegenic cells from various organisms, such as human, non-human primate (e.g., cynomolgus monkey, rhesus monkey, etc. ) , mouse, rat, cat, dog, hamster, rabbit, pig, cow, goat, sheep, horse, donkey, deer, mammal, bird, reptile, amphibian, fish, arthropod, mollusk, echinoderm, cnidarian, nematode, annelid, platyhelminth, etc.

The methods described herein are applicable for a variety of tissues, including, but are not limited to tissues derived from germline, endoderm, mesoderm, or ectoderm. In some embodiments, the tissue is a connective tissue (for example, loose connective tissue, dense connective tissue, elastic tissue, reticular connective tissue and fat tissue) , a muscle tissue (for example, skeletal muscle, smooth muscle and cardiac muscle) , urogenital tissue, gastrointestinal tissue, lung tissue, bone tissue, nerve tissue and epithelial tissue (for example, a single layer of epithelial and stratified epithelium) . In some embodiments, the tissue is of an organ selected from the group consisting of heart, liver, kidney, lung, stomach, intestine, bladder, and brain. In some embodiments, the tissue is a liver tissue. In some embodiments, the tissue is a heart tissue. In some embodiments, the tissue is a skin tissue. In some embodiments, the tissue is a hair follicle.

In some embodiments, the tissue is skeletal muscle. According to certain embodiments, compositions disclosed herein may be administered in conjunction with a strength training regime. As will be appreciated by a person having skill in the art, administration of effective amounts of the disclosed compositions results in improved strength and improved athletic performance or ergogenesis in the subject. In one aspect, the disclosed compounds inhibit muscle atrophy. In a further aspect, the disclosed compounds increase muscle mass. In a still further aspect, the disclosed compounds induce muscle hypertrophy. In a yet further aspect, the disclosed compounds inhibit muscle atrophy and increase muscle mass. In an even further aspect, the disclosed compounds inhibit of muscle atrophy and induce muscle hypertrophy.

In some embodiments, the tissue is from an individual. In some embodiments, the tissue is from an aged individual, such as a rodent of at least 1 years old, 1.5 years old, 2 years old, or more, or a human of at least about any one of 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 or more years old. In some embodiments, the tissue is not from an aged individual, such as a rodent of at most 1 years old, 0.5 years old, or less, or a human of at most about any one of 40, 35, 30, 25, 20 or less years old.

III. Composition of matter for treatment

The present application further provides compositions of matter for treating or preventing disease or condition associated with a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. Suitable diseases or conditions include, but are not limited to, sarcopenia, cachexia, disuse atrophy, myopathies, alopecia, cardiomyopathies, chronic heart failure, chronic kidney failure, skin wrinkling, balding, macular degeneration, fatty liver disease, liver steatosis, steatohepatitis, type 2 diabetes (T2D) , chronic obstructive pulmonary disease (COPD) , osteoarthritis, osteoporosis, fibrosis, cirrhosis, chronic hepatic insufficiency, idiopathic pulmonary fibrosis, cardiac fibrosis, uterine fibrosis, scarring, arthrofibrosis, keloids, myelofibrosis, retroperitoneal fibrosis, scleroderma, sclerosis, chronic wounds (such as diabetic foot ulcer) , chronic dermal fibrosis, cutaneous fibrosis, skin aging, fatty liver disease, nonalcoholic steatohepatitis (NASH) , hair loss, tissue atrophy, menopause, ovarian aging, primary ovarian insufficiency, endometrial hyperplasia, adenomyosis, and any other disease resulting from injury, surgery, cancer, congenital, developmental, and environmental loss or damage to tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the disease or condition is disuse atrophy. In some embodiments, the composition of matter for treating or preventing disease or condition associated with a tissue, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids and/or peptides. Suitable diseases or conditions include, but are not limited to, sarcopenia, cachexia, disuse atrophy, myopathies, alopecia, cardiomyopathies, chronic heart failure, chronic kidney failure, skin wrinkling, balding, macular degeneration, liver steatosis, fatty liver disease, steatohepatitis, type 2 diabetes (T2D) , chronic obstructive pulmonary disease (COPD) , osteoarthritis, osteoporosis, fibrosis, cirrhosis, chronic hepatic insufficiency, idiopathic pulmonary fibrosis, cardiac fibrosis, uterine fibrosis, scarring, arthrofibrosis, keloids, myelofibrosis, retroperitoneal fibrosis, scleroderma, sclerosis, chronic wounds (such as diabetic foot ulcer) , chronic dermal fibrosis, cutaneous fibrosis, skin aging, nonalcoholic steatohepatitis (NASH) , hair loss, tissue atrophy, menopause, ovarian aging, primary ovarian insufficiency, endometrial hyperplasia, adenomyosis, and any other disease resulting from injury, surgery, cancer, congenital, developmental, and environmental loss or damage to tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the disease or condition is disuse atrophy. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

Methods of Administration

In some embodiments, there is provided a method of treating a disease or condition associated with a tissue in an individual, comprising administering an effective amount of a pharmaceutical composition comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, the disease or condition is tissue injury. In some embodiments, the disease or condition is tissue degeneration. In some embodiments, the disease or condition is tissue fibrosis. In some embodiments, the disease or condition is aging. In some condition the disease or condition is inflammaging. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm, and can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair, epithelial, urogenital, cervix, uterus, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the disease or condition is disuse atrophy. In some embodiments, the possible route of administration of the composition of matter includes but is not limited to: oral, sublingual, buccal, nasal, inhalation, intratracheal, intravenous, intraarterial, intracoronary, intrathecal, intramuscular, intraperitoneal, intramyocardial, trans-endocardial, trans-epicardial, subcutaneous, transdermal, vaginal, rectal, or otic. In some embodiments according to any one of the methods of treatment described above, the disease or condition is associated with tissue damage or tissue degeneration or tissue aging or can benefit from new tissue regeneration or new tissue replacement and selected from the group consisting of but not limited to sarcopenia, cachexia, disuse atrophy, myopathies, alopecia, cardiomyopathies, chronic heart failure, chronic kidney failure, skin wrinkling, balding, macular degeneration, liver steatosis, fatty liver disease, steatohepatitis, type 2 diabetes (T2D) , chronic obstructive pulmonary disease (COPD) , arthritis, rheumatoid arthritis, periodontitis, cataracts, osteoporosis, fibrosis, cirrhosis, chronic hepatic insufficiency, idiopathic pulmonary fibrosis, cardiac fibrosis, uterine fibrosis, scarring, arthrofibrosis, keloids, myelofibrosis, retroperitoneal fibrosis, scleroderma, sclerosis, chronic wounds (such as diabetic foot ulcer) , chronic dermal fibrosis, cutaneous fibrosis, skin aging, nonalcoholic steatohepatitis (NASH) , hair loss, tissue atrophy, menopause, ovarian aging, primary ovarian insufficiency, endometrial hyperplasia, adenomyosis, sarcopenia, neurodegenerative diseases and any other disease resulting from injury, surgery, cancer, congenital, developmental, and environmental loss or damage to tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the disease or condition is disuse atrophy. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, there is provided a method of treating a disease or condition associated with a tissue in an individual, comprising administering an effective amount of a pharmaceutical composition comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and/or amino acids and/or peptides. In some embodiments, the disease or condition is tissue injury. In some embodiments, the disease or condition is tissue degeneration. In some embodiments, the disease or condition is tissue fibrosis. In some embodiments, the disease or condition is aging. In some condition the disease or condition is inflammaging. In some embodiments, the tissue is derived from germline, endoderm, mesoderm, or ectoderm, and can be chosen from any of the following: connective, muscle, heart, lung, liver, fat, hair, epithelial, urogenital, cervix, uterus, gastrointestinal, bone, nerve, kidney, bladder, and brain. In some embodiments, the tissue is muscle tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the disease or condition is disuse atrophy. In some embodiments, the possible route of administration of the composition of matter includes but is not limited to: oral, sublingual, buccal, nasal, inhalation, intratracheal, intravenous, intraarterial, intracoronary, intrathecal, intramuscular, intraperitoneal, intramyocardial, trans-endocardial, trans-epicardial, subcutaneous, transdermal, vaginal, rectal, or otic. In some embodiments according to any one of the methods of treatment described above, the disease or condition is associated with tissue damage or tissue degeneration or tissue aging or can benefit from new tissue regeneration or new tissue replacement and selected from the group consisting of but not limited to sarcopenia, cachexia, disuse atrophy, myopathies, alopecia, cardiomyopathies, chronic heart failure, chronic kidney failure, skin wrinkling, balding, macular degeneration, liver steatosis, fatty liver disease, steatohepatitis, type 2 diabetes (T2D) , chronic obstructive pulmonary disease (COPD) , arthritis, rheumatoid arthritis, periodontitis, cataracts, osteoporosis, fibrosis, cirrhosis, chronic hepatic insufficiency, idiopathic pulmonary fibrosis, cardiac fibrosis, uterine fibrosis, scarring, arthrofibrosis, keloids, myelofibrosis, retroperitoneal fibrosis, scleroderma, sclerosis, chronic wounds (such as diabetic foot ulcer) , chronic dermal fibrosis, cutaneous fibrosis, skin aging, nonalcoholic steatohepatitis (NASH) , hair loss, tissue atrophy, menopause, ovarian aging, primary ovarian insufficiency, endometrial hyperplasia, adenomyosis, sarcopenia, neurodegenerative diseases and any other disease resulting from injury, surgery, cancer, congenital, developmental, and environmental loss or damage to tissue. In some embodiments, the disease or condition is associated with involuntary weight loss, such as but not limited to sarcopenia and cachexia. In some embodiments, the condition or disease is disuse atrophy. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3 In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

Generally, dosages, schedules, and routes of administration of the compositions may be determined according to the size and condition of the individual, and according to standard pharmaceutical practice. Exemplary routes of administration include but is not limited to and may consists of combinations of: oral, rectal, nasal, topical (including buccal and sublingual) , transdermal, vaginal, parenteral (including intramuscular, subcutaneous and intravenous) , inhalation, intratracheal, intravenous, intraarterial, intracoronary, intrathecal, intraperitoneal, intramyocardial, trans-endocardial, trans-epicardial, subcutaneous, topical, transdermal, or otic. In some embodiments, the composition is administered subcutaneously. In some embodiments, the composition is administered intramuscularly. In some embodiments, the composition is administered by injection. In some embodiments, the composition is administered to the individual systemically. In some embodiments, the composition is administered to the individual orally. In some embodiments, the composition is administered via the topical or transdermal route.

Pharmaceutical compositions

The present application provides compositions such as pharmaceutical compositions useful for any one of the methods of treatment described herein.

The pharmaceutical compositions may comprise one or more pharmaceutically acceptable carrier. As used herein, by “pharmaceutically acceptable” or “pharmacologically compatible” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration. Techniques for formulation and administration of drugs may be found in "Remington's Pharmaceutical Sciences, " Mack Publishing Co., Easton, PA, latest edition, which is incorporated herein by reference.

The pharmaceutical compositions described herein may include other agents, excipients, or stabilizers to improve properties of the composition. Examples of pharmaceutically acceptable excipients include stabilizers, lubricants, surfactants, diluents, anti-oxidants, binders, coloring agents, bulking agents, emulsifiers, or taste-modifying agents. In preferred embodiments, pharmaceutical compositions according to the embodiments are sterile compositions. Pharmaceutical compositions may be prepared using compounding techniques known or that become available to those skilled in the art. The final form may be sterile and may also be able to pass readily through an injection device such as a hollow needle. The proper viscosity may be achieved and maintained by the proper choice of solvents or excipients. In some embodiments, the composition is suitable for administration to a human.

The pharmaceutical compositions and compounds described herein may be formulated as solutions, emulsions, suspensions, dispersions, or inclusion complexes such as cyclodextrins in suitable pharmaceutical solvents or carriers, or as pills, tablets, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms.

The formulations may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association the active ingredient with one or more pharmaceutically acceptable carriers, like liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired formulation.

Nutraceutical Compositions

In some embodiments, the said composition, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, can be administered in the form of a dietary supplement, a nutritional supplement or a nutraceutical product. In some embodiments, the compositions can be a dietary supplement that can be ingested, injected, or absorbed through the skin. Preferably, the compositions can be administered in one or more doses per day. In some embodiments, the composition can be in a solid form or a liquid form or in a suspension which can be ingested or infused into the body. The composition can be ingested by humans in an amount of between 0.01 grams and 1000 grams or more per day, which may be taken in one or more parts throughout the day. In animals, including humans, the daily intake will be adjusted by body weight. In some example embodiments, the said composition comprises of 5mg/kg to 30mg/kg of compound B a salt, solvate, tautomer, analog or stereoisomer thereof and 3mg/kg to 15mg/kg of leucine or isoleucine or combinations thereof to be administered daily. (note: mg/kg refers to mg of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof or amino acids/peptides administered per kg body weight of subject to be administered) In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

In some embodiments, the compositions are applied to a body for at least three days, from 3 days to 2 weeks, from 2 weeks to 4 weeks, or longer. In certain regimens, the daily dosages are gradually increased or decreased. This can be done daily, every couple of days, every three days, every four days, every five days, every six days, or weekly. In some embodiments, the composition comprises of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids or peptides. In some embodiments, the amino acids can be chosen from leucine or isoleucine or combinations thereof. In some embodiments, peptides consist of more than one unit of leucine, isoleucine or combinations thereof. In some embodiments, compound B and the amino acids and/or peptides are administered in a single dosage form. In some embodiments, compound B and the amino acids/peptides are administered in separate dosage forms. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

Cosmeceutical Compositions or Cosmetics

In some embodiments, the said composition, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, can be administered in the form of a cosmeceutical product or cosmetic that can enhance the external appearance of an individual. In some embodiments, the said compositions can reduce or reverse or prevent wrinkles. In some embodiments, the said compositions can enhance the beauty of an individual. In some embodiments, the said compositions can enhance the beauty of an individual by increasing skeletal muscles underneath the skin. In some embodiments, the said compositions can be ingested, injected or absorbed through the skin. In some embodiments, the said composition can be applied onto the skin and absorbed through the skin. In some embodiments, the said composition can be applied daily, multiple times a day, once in two days, once in three days, once in four days, once in five days, once in 6 days, once a week or once a fortnight. In some embodiments, compound B can be represented by formula (1) , formula (4) or formula (5) . In some preferred embodiments, compound B can be represented by formula (2) or formula (3) . In some embodiments, compound B can be represented by any of the following formulas: 21, 22, 23, 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512. In some preferred embodiments, compound B can be represented by formula 22, In some preferred embodiments, the said composition comprises of amino acid and peptides in addition to compound B, represented as formula 22. In some preferred embodiments, the said composition of matter comprises both compound B represented as formula 22 and leucine.

Compound B and Amino Acids/Peptides

In some embodiments, there is provided a composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula (1) as shown below:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms. In some embodiments, V and G comprises any of the following groups but not limited to: hydroxyl, carboxyl, carbamate, amide, thiol, thioester, phosphoesters, phosphodiester, phosphoramide, phosphoramidite, phosphoramidic acid, amino acid, sugar, lipid. In some embodiments, V and G comprises hydrolysable chemical groups, that can hydrolyze under physiological conditions. In some embodiments, V and/or G comprises ionic groups. In some embodiments, V and/or G comprises non-ionic groups. In some embodiments, V and/or G comprises subgroups of amino acids. In some embodiments, V and/or G comprises any number of leucine and/or isoleucine subunits or combinations thereof.

In some embodiments, compound B can be further represented by formula (2) as shown below:

Where R ₁ is a hydrocarbon that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and X can be selected from any of the following: COOH, OH, SH, NH ₂, amide, esters, phosphate, phosphonate, sulphate, nitro, heteroalkyl, heteroaryl, heteroalkenyl, heteroalkynyl. In some embodiments, R ₁ can be represented by –CH ₂ (n) -, where 1<n<6. In some embodiments, R ₁ is –CH ₂CH ₂-. In some embodiments, X is COOH.

In some embodiments, compound B can be further represented by any of following formulas or chemical structures displayed in Table 1 below.

Table 1: Formula or chemical structure representing compound B

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms. In some embodiments, V and G comprises any of the following groups but not limited to: hydroxyl, carboxyl, carbamate, amide, thiol, thioester, phosphoesters, phosphodiester, phosphoramide, phosphoramidite, phosphoramidic acid, amino acid, sugar, lipid. In some embodiments, V and G comprises hydrolysable chemical groups, that can hydrolyze under physiological conditions. In some embodiments, V and/or G comprises ionic groups. In some embodiments, V and/or G comprises nonionic groups. In some embodiments, V and/or G comprises subgroups of amino acids. In some embodiments, V and/or G comprises any number of leucine and/or isoleucine subunits or combinations thereof. In some embodiments, some examples of compound B include but is not limited to 4-Phosphopantothenate, 4-Phosphopantothenoylcysteine, 4-Phosphopantetheine, Dephospho-Coenzyme A and Coenzyme A. In some embodiments, there is provided a composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula (1) as shown below:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms. In some embodiments, V and G comprises any of the following groups but not limited to: hydroxyl, carboxyl, carbamate, amide, thiol, thioester, phosphoesters, phosphodiester, phosphoramide, phosphoramidite, phosphoramidic acid, amino acid, sugar, lipid. In some embodiments, V and G comprises hydrolysable chemical groups, that can hydrolyze under physiological conditions. In some embodiments, V and/or G comprises ionic groups. In some embodiments, V and/or G comprises nonionic groups. In some embodiments, V and/or G comprises subgroups of amino acids. In some embodiments, V and/or G comprises any number of leucine and/or isoleucine subunits or combinations thereof.

In some embodiments, there is provided a composition, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula (3) as shown below:

Where V ₁ consists of any amount of carbon, hydrogen, phosphorus, sulphur, oxygen, or nitrogen atoms and V ₂ is a hydrogen or a hydrocarbon (i.e CH ₃) group. In some embodiment, V ₁ may be ionic. In some embodiment, V ₁ is nonionic. In some embodiments, V ₁ can be chosen but not limited to any of the following groups: acetyl, carboxyl, carbamate, phosphoester, phosphodiester, phosphoramidite, phosphoramidic acid, phosphoramide, ethylene glycol, sugar moiety and/or glycol. In some embodiments, V ₁ is a phosphoramide or carbamate comprising of one or two functionalized amino acid moiety. In some embodiments, V ₁ comprises nonionic amino acids, which may be polar or nonpolar. In some embodiments, V ₁ comprises of one or more subunits of leucine or/and isoleucine or combinations thereof.

In some embodiments, compound B can be further represented by any of following formulas or chemical structures displayed in Table 2 below.

Table 2: Formula or chemical structure representing compound B

In some embodiments, there is provided a composition compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula (4) as shown below:

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.

In some embodiments, there is provided a composition comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula or chemical structure (5) as shown below:

Where L is a hydrolysable linker. The linker may be branched or linear. The linker may also include functional handles such as -O-, -S-, -NR-, - (C=O) -, -SO-, -SO ₂, phosphodiester, maleimide, N-hydroxy-succinimide esters, amines, and carboxylic acids, for conjugation, modification, and crosslinking. The linker may be hydrophobic, hydrophilic, or amphiphilic. Hydrophobic linker may consist of but is not limited to alkyl, allyl, aryl, cycloalkyl, heterocyclic, heteroaryl groups or combinations thereof. Examples of hydrophilic linkers can be formed primarily from carbon, hydrogen, and oxygen and/or nitrogen and/or sulphur and/or phosphorous. In some embodiments, hydrophilic linkers comprise one or more amino acids, one or more aspartic acids, one or more glutamic acids, one or more arginines, one or more beta amino alanines, one or more divalent 1, 4-piperazines, one or more triazole-linked polyhydroxyl group containing linkers, one or more ethylene glycols, one or more amide-linked polyhydroxyl group containing linkers, one or more EDTA derivatives, one or more alkoxy groups or combinations thereof. In some embodiments, aforementioned linker is hydrolysable. Examples of hydrolysable linkers consists of but not limited to disulphides, hydrazones, pH-sensitive linkers, peptides (such as Val-Cit-PABC) , glucuronides (such as glucaronide-MABC) , dimethacrylate (such as dimethyldi (methacryloyloxy-1-ethoxy) silane, symmetrical and/or unsymmetrical ether carboxylic acids, amines, amide diols, amine polyols, diazo, sulphonates, and isocyanates. In some embodiments, L does not exist and Z is directly linked to the rest of the molecule in the form of an amide linkage. In some embodiments, Z is an amino acid or a peptide. In some embodiments, the amino acid can be either leucine or isoleucine. In some embodiments, the peptide consists of at least one or several units of leucine or/and isoleucine.

In some exemplary but non-limiting embodiments, compound B can be represented by formula or chemical structure (5) as shown below, where –means that L does not exist and Z is linked to rest of the molecule via an amide bond:

In some embodiments, there is provided a composition, comprising of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof. In some embodiments, compound B can be represented by formula (6) as shown below:

Where V ₁ consists of any amount of carbon, hydrogen, phosphorus, sulphur, oxygen, nitrogen atoms. In some embodiments, V ₁ can be chosen but not limited to any of the following groups: acetyl, phosphor, carboxyl,

In some embodiments, the composition comprises of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof and amino acids or peptides. In some embodiments, the amino acids can be chosen from leucine or isoleucine or combinations thereof. In some embodiments, peptides consist of more than one unit of leucine, isoleucine or combinations thereof. In some embodiments, compound B and the amino acids and/or peptides are administered in a single dosage form. In some embodiments, compound B and the amino acids/peptides are administered in separate dosage forms. The composition may be formulated for any of the following methods of administration or combinations thereof: oral, rectal, nasal, intratracheal, intracoronary, intrathecal, intraperitoneal, intramyocardial, trans-endocardial, topical (including buccal and sublingual) , transdermal, vaginal, rectal, otic, or parenteral (including intramuscular, subcutaneous, intraarterial, and intravenous) administration in liquid or solid form or in a form suitable for administration by inhalation or insufflation. In some embodiments, the composition is formulated for intramuscular or subcutaneous administration. In some embodiments, the composition is formulated for oral administration.

For oral administration, the composition may be provided in a solid form, or as a solution, emulsion, or suspension. For example, the pharmaceutical composition may be formulated in the form of tablets, granules, fine granules, powders, capsules, caplets, soft capsules, pills, oral solutions, syrups, dry syrups, chewable tablets, troches, effervescent tablets, drops, suspension, fast dissolving tablets, oral fast-dispersing tablets, etc.

Compositions suitable for oral administration may conveniently be presented as discrete units such as capsules, including soft gelatin capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution, a suspension or as an emulsion, for example as syrups, elixirs or self-emulsifying delivery systems (SEDDS) . The active ingredients may also be presented as a bolus, electuary or paste. Tablets and capsules for oral administration may contain conventional excipients such as binding agents, fillers, lubricants, disintegrants, or wetting agents. The tablets may be coated according to methods well known in the art. Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils) , or preservatives.

Transdermal formulations may include single-layer/multi-layer drug-in-adhesive transdermal patches, matrix types, lotions, creams, ointments, liquid or gel reservoir delivery systems. In some embodiments, transdermal formulation may either come in the form of a metered liquid spray, gel or other topical formulation to the skin that, upon evaporation or absorption, can drive small lipophilic drugs into the stratum corneum. In some embodiments, gels used in transdermal formulation may include but is not limited to hydrogels, oleogels, organogels, niosomal gels, proniosomal gels, emulgels, bigels, biphasic gels, aerogels, xerogels or combinations thereof. In some embodiments, transdermal formulations and methods may include methods to modulate or promote transdermal delivery, such as but not limited to conventional chemical enhancers, iontophoresis, sonophoresis, electroporation, thermal energy methods, skin metabolism inhibitors, liposomes, ethosomes, transfersomes, aquasomes, dendrimers, nanoemulsions, polymeric nanoparticles, solid lipid nanoparticles, microneedles, microchips, non-cavitational ultrasound or combinations thereof. Examples of chemical permeation enhancers include but is not limited to short-chain alcohols (e.g. ethanol, isopropanol) , long-chain alcohols (e.g. Decanol, Octanol) , glycols (e.g. ethylene glycol, propylene glycol) , amides (e.g.

(1-dodecylazacycloheptan2-one or laurocapram) , fatty acids (e.g. Lauric acid, Oleic acid, Linoleic acid ) , alkyl esters (e.g. ethyl acetate, butyl acetate, methyl acetate) , fatty acid esters (Isopropyl myristate, Isopropyl palmitate) , ether alcohols (e.g.

(diethylene glycol monoethyl ether) , anionic surfactants (Sodium lauryl sulphate (SLS) ) , cationic surfactants (Benzalkonium chloride, Cetylpyridinium chloride, Cetyltrimethylammonium bromide) , nonionic surfactants (e.g. Polysorbates (

20,

80, etc. ) ) , zwitterionic surfactants (e.g. Dodecyl betaine) , sulphoxides (e.g. Dimethyl sulphoxide (DMSO) Decylmethyl sulphoxide (DCMS) ) , sulphoxide analogs, essential oils (e.g. Eucalyptus Ylang ylang Chenopodium) , terpines and terpine derivatives (e.g. d-Limonene l-Menthol 1, 8-Cineole) , Pyrrolidones (e.g. N-methyl-1-2-pyrrolidone (NMP) , 2-pyrrolidone (2P) ) , Oxazolidines (e.g. 4-decyloxazolidin-2-one ) , phospholipids (e.g. Phosphatidylcholine (PC) ) , enzymes (e.g. Acid phosphatase, papain, phospholipase C) . Transdermal formulations also typically include excipients and permeation enhancers. Typical excipients and permeation enhancers are known in the art.

The compositions according to the application may also be formulated for parenteral administration (e.g. by injection, for example bolus injection or continuous infusion) and may be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredients may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.

Compositions suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art, and the suppositories may be conveniently formed by admixture of the active compound (s) with the softened or melted carrier (s) followed by chilling and shaping in moulds.

V. Kits and articles of manufacture

The application further provides kits, formulations, unit dosages, and articles of manufacture for use in any one of the methods of muscle regeneration in vitro or in vivo, and methods of treatment described herein.

The kits may also comprise instructions relating to the use of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof with or without amino acids/peptides in any one of the methods described herein. In some embodiments, the kit further comprises an instructional manual, such as a manual describing a protocol according to any one of the methods of muscle regeneration, or methods of treatment described herein. The instructions may also include information on dosage, dosing schedule, and routes of administration of compound B, a salt, solvate, tautomer, analog or stereoisomer thereof with or without amino acids/peptides using the kit for the intended treatment.

Also provided are unit dosage forms comprising the compound B, a salt, solvate, tautomer, analog or stereoisomer thereof with or without amino acids/peptides and formulations described herein. These unit dosage forms can be stored in a suitable packaging in single or multiple unit dosages and may also be further sterilized and sealed. In some embodiments, the composition (such as pharmaceutical composition) is contained in a single-use vial, such as a single-use sealed vial. In some embodiments, the composition (such as pharmaceutical composition) is contained in a multi-use vial. In some embodiments, the composition (such as pharmaceutical composition) is contained in bulk in a container.

EXAMPLES

EXAMPLE 1. Compounds

Unless stated otherwise, compounds listed above were purchased from either Sigma Aldrich, ZINC, THE BioTek, AliChem, LabNetwork, MuseChem, AKos Consulting & Solutions GmbH, BLD Pharm, AA BLOCKS LLC, Aurum Pharmatech LLC, or ARONIS.

Synthesis of Dipeptides

Dipeptides were synthesized by condensing either Fmoc-L-leucine or Fmoc-L-Isoleucine (1.0 eq) with either L-Leucine tert butyl ester hydrochloride (1.0 eq) or L-Isoleucine tert butyl ester hydrochloride (1.0 eq) or L-Leucine methyl ester (1.0 eq) or L-Isoleucine (1.0 eq) in the presence of EDC (1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide) and HOBt (N-Hydroxybenzotriazole) to yield Fmoc-L-Leucyl-L-Leucine tert butyl ester hydrochloride (LLtbutyl) , Fmoc-L-Isoleucyl-L-IsoLeucyl-tert butyl ester hydrochloride (IItbutyl) , Fmoc-L-Isoeucyl-L-Leucine tert butyl ester hydrochloride (ILtbutyl) , Fmoc-L-Leucyl-L-IsoLeucyl-tert butyl ester hydrochloride (LItbutyl) Fmoc-L-Leucyl-L-Leucine methyl ester (LLMe) , Fmoc-L-Isoleucyl-L-IsoLeucyl-methyl ester (IIMe) , Fmoc-L-Isoeucyl-L-Leucine methyl ester (ILMe) , Fmoc-L-Leucyl-L-IsoLeucyl-methyl ester (LIMe) respectively. The respective dipeptides were purified with column chromatography. To prepare the above dipeptides for use, the Fmoc groups were removed by adding piperazine to the above dipeptides to yield the respective amines.

Synthesis of t-butyl pantothenate

t-butyl pantothenate is prepared by adding pantothenic acid to (BOC) ₂O and DMAP in accordance to the protocol detailed in Gooen and

2003. The resultant t-butyl pantothenate was purified by column chromatography.

Synthesis of 32, 33 and 34

The synthesis protocol was modified from Magolda and Johnson, 1985. Stoichiometric amounts of phosphorous chloride were added to methyl pantothenate and trimethylamine under nitrogen in anhydrous ether to generate the dichlorophosphate. The trimethylamine hydrochloride was filtered, then diluted and cooled to 0℃ and 2 equiv of trimethylamine and a 1: 1 mixture of L-Leucine t-butyl ester and L-IsoLeucine t-butyl ester were added. After 12h of stirring at room temperature, the final product was purified by column chromatography to yield 3 different analogs of 32, 33 and 34 respectively.

Synthesis of 36, 37 and 318

The synthesis protocol was modified from Magolda and Johnson, 1985. Stoichiometric amounts of phosphorous chloride were added to t-butyl pantothenate and trimethylamine under nitrogen in anhydrous ether to generate the dichlorophosphate. The trimethylamine hydrochloride was filtered, then diluted and cooled to 0℃ and 2 equiv of trimethylamine and a 1: 1 mixture of L-Leucine t-butyl ester and L-IsoLeucine t-butyl ester were added. After 12h of stirring at room temperature, the final product was purified by column chromatography to yield 3 different t-butyl esterified analogs of 36, 37 and 318 respectively. (Protocol modified from Magolda and Johnson, 1985) To yield 36, 37 and 318, the abovementioned compounds were dissolved in dichloromethane and treated with trifluoroacetic acid at room temperature for 1h.

Synthesis of 35, 38, 39, 310, 311, 312, 315

To prepare the above compounds, one-pot condensation of the respective methyl ester hydrochloride of the various L amino acids (L-Leucine methyl ester, L-Isoleucine methyl ester, L-Alanine methyl ester, L-Phenylalanine methyl ester, L-Threonine methyl ester, L-Valine methyl ester, IL-Me) (1.0 eq) with methyl phosphorodichloridate (1.0 eq) in the presence of triethylamine as base and dichloromethane as solvent. Trapping of the intermediate thus formed by addition of methyl pantothenate (1.1 eq) or pantothenic acid followed by silica gel purification afforded 35, 39, 310, 311, 312, 313, 314 as an approximately 1: 1 mixture of diastereomers. (Protocol modified from doi: 10.1371/journal. pone. 0192028)

Synthesis of 313, 314, 316, 317

To prepare the above compounds, one-pot condensation of the respective t-butyl ester of the various L amino acids (L-Isoleucine-tert-butyl ester hydrochloride, L-Leucine-t-butyl ester hydrochloride, ILtbutyl, LLtbutyl) (1.0 eq) with methyl phosphorodichloridate (1.0 eq) in the presence of triethylamine as base and dichloromethane as solvent. Trapping of the intermediate thus formed by addition of t-butyl pantothenate (1.1 eq) followed by silica gel purification afforded t-butyl esterified phosphoamides as an approximately 1: 1 mixture of diastereomers. To yield the 313, 314, 316 and 317, the products from the above reactions were dissolved in dichloromethane and TFA was added to the mixture and stirred for an hour. The resulting product was purified by column chromatography. (Protocol modified from doi: 10.1371/journal. pone. 0192028)

Synthesis of 321, 322, 323, 324, 325, 326, 327, 328, 329, 330

In a typical procedure, carbonyldiimidazole (30 mg, 0.18 mmol) was suspended in anhydrous dichloromethane (0.5 ml) and the mixture was cooled to 0℃. Methyl Pantothenate (42 mg, 0.18 mmol) was slowly added as a solution in dichloromethane (0.5 ml) . The mixture was stirred at room temperature for 1 h. The respective amino acids/dipeptides (L-Isoleucine methyl ester, L-leucine methyl ester, L-Isoleucine t-butyl ester hydrochloride, L-leucine t-butyl ester hydrochloride, ILMe, LLMe, IIMe, ILtbutyl, LLtbutyl, IItbutyl) were added (0.18 mmol) and the mixture was stirred at room temperature for 6 h. Ethyl acetate was added, and the mixture was washed four times with HCl 10%, and once with brine. The organic layer was dried over MgSO4, filtered and column chromatography was performed to yield 321, 322, 325, 326, 327 and 328 respectively. (Protocol modified from doi: 10.1016/S0040-4039 (01) 00991-1)

Synthesis of 323, 324, 329, 330

In a typical procedure, carbonyldiimidazole (30 mg, 0.18 mmol) was suspended in anhydrous dichloromethane (0.5 ml) and the mixture was cooled to 0℃. T-butyl Pantothenate (49.5 mg, 0.18 mmol) was slowly added as a solution in dichloromethane (0.5 ml) . The mixture was stirred at room temperature for 1 h. The respective amino acids/dipeptides (L-Isoleucine t-butyl ester hydrochloride, L-leucine t-butyl ester hydrochloride, ILtbutyl, LLtbutyl, IItbutyl) were added (0.18 mmol) and each mixture was stirred at room temperature for 6 h. Ethyl acetate was added, and the mixture was washed four times with HCl 10%, and once with brine. The organic layer was dried over MgSO4, filtered and column chromatography was performed to yield the esterified carbamates. This include the t-butyl esterified versions of 323, 324, 328, 329 and 330. To yield 323, 324, 328, 329 and 330, the above t-butyl-containing carbamates obtained from above were dissolved in dichloromethane and TFA was added and the mixture was stirred at room temperature for about 1h and purified subsequently. (Protocol modified from doi: 10.1016/S0040-4039 (01) 00991-1)

Synthesis of 41

In a typical procedure (Smietana et al, 2003, Evans et al., 2002) , tetrabutylammonium bromide is heated to 105℃, 3-methyl-2-butanone (1.0eq) was added, followed by (bistrimethylsilyl) acetamide (BSA) (1.2eq) . The mixture was stirred for 4h at 105℃and directly distilled under reduced pressure without any workup to give the pure silyl enol ether. A dry flask was charged with ScCl3 (thf) 3 (0.15 equiv) and t-Bu-pyridyl-bis (oxazolinyl) ligand (0.17 equiv) in an inert atmosphere (N ₂) glove box. In a separate flask, also in an inert atmosphere (N ₂) glove box, was charged AgSbF6 (0.14 equiv) . Both flasks were brought out of the glove box and the flask containing the metal/ligand was charged with CH ₂Cl ₂ and stirred at room temperature for 1 h. The resulting solution was transferred to the flask containing AgSbF6 via syringe and the mixture stirred for 30 minutes followed by cooling to -78℃. Ethyl glyoxylate (1.5 equiv) , the enolsilane from above reaction (1.0 equiv) , and TMS-Cl (2 equiv) were added sequentially and the reaction stirred for 16h at -35 ℃. After the reaction was complete, the mixture was filtered through silica with Et ₂O and the silyl ether was hydrolyzed with 1N HCl in EtOAc (30 min, 25℃) to give the hydroxy ester which was purified by flash chromatography. To obtain 41, the following protocol was used. To an oven dried flask was added Me4NHB (OAc) 3 (8.4 equiv) and MeCN/AcOH (1: 1 v/v) to afford a 0.9 M solution which was stirred for 30 min at room temperature before cooling to -20℃. To this mixture, was added a solution of hydroxy-ester (1.0 equiv) in MeCN (0.65 M) and aged for 1 hr at -20℃ before warming to 0℃ and aging for an additional 16 hr. To the reaction was added saturated Rochelle’s salt and saturated NaHCO3 and then extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and washed with NaHCO3 (10 mL) . The aqueous layer was back-extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and concentrated in vacuo to afford a colorless oil which was transferred to a dry flask and charged with benzene (0.23 mL) ,

MS (25 mg) , and p-TSA (0.5 equiv) . The reaction was stirred at room temperature for 30 min. and diluted with Et2O (2 mL) . Triethylamine (6 drops) was added to the mixture which was then filtered through a plug of silica gel and flushed with Et2O (50 mL) . Concentration of the solvent in vacuo provided the desired product.

Synthesis of 42

In a typical procedure (Smietana et al, 2003, Evans et al., 2002) , tetrabutylammonium bromide is heated to 105℃, 2-methyl-3-pentanone (1.0eq) was added, followed by (bistrimethylsilyl) acetamide (BSA) (1.2eq) . The mixture was stirred for 4h at 105℃and directly distilled under reduced pressure without any workup to give the pure silyl enol ether. A dry flask was charged with ScCl3 (thf) 3 (0.15 equiv) and t-Bu-pyridyl-bis (oxazolinyl) ligand (0.17 equiv) in an inert atmosphere (N ₂) glove box. In a separate flask, also in an inert atmosphere (N ₂) glove box, was charged AgSbF6 (0.14 equiv) . Both flasks were brought out of the glove box and the flask containing the metal/ligand was charged with CH ₂Cl ₂ and stirred at room temperature for 1 h. The resulting solution was transferred to the flask containing AgSbF6 via syringe and the mixture stirred for 30 minutes followed by cooling to -78℃. Ethyl glyoxylate (1.5 equiv) , the enolsilane from above reaction (1.0 equiv) , and TMS-Cl (2 equiv) were added sequentially and the reaction stirred for 16h at -35℃. After the reaction was complete, the mixture was filtered through silica with Et ₂O and the silyl ether was hydrolyzed with 1N HCl in EtOAc (30 min, 25℃) to give the hydroxy ester which was purified by flash chromatography. To obtain 42, the following protocol was used. To an oven dried flask was added Me4NHB (OAc) 3 (8.4 equiv) and MeCN/AcOH (1: 1 v/v) to afford a 0.9 M solution which was stirred for 30 min at room temperature before cooling to -20℃. To this mixture, was added a solution of hydroxy-ester (1.0 equiv) in MeCN (0.65 M) and aged for 1 hr at -20℃ before warming to 0℃ and aging for an additional 16 hr. To the reaction was added saturated Rochelle’s salt and saturated NaHCO3 and then extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and washed with NaHCO3 (10 mL) . The aqueous layer was back-extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and concentrated in vacuo to afford a colorless oil which was transferred to a dry flask and charged with benzene (0.23 mL) ,

Synthesis of 44

In a typical procedure (Smietana et al, 2003, Evans et al., 2002) , tetrabutylammonium bromide is heated to 105℃, 2-methyl-3-hexanone (1.0eq) was added, followed by (bistrimethylsilyl) acetamide (BSA) (1.2eq) . The mixture was stirred for 4h at 105℃and directly distilled under reduced pressure without any workup to give the pure silyl enol ether. A dry flask was charged with ScCl3 (thf) 3 (0.15 equiv) and t-Bu-pyridyl-bis (oxazolinyl) ligand (0.17 equiv) in an inert atmosphere (N ₂) glove box. In a separate flask, also in an inert atmosphere (N ₂) glove box, was charged AgSbF6 (0.14 equiv) . Both flasks were brought out of the glove box and the flask containing the metal/ligand was charged with CH ₂Cl ₂ and stirred at room temperature for 1 h. The resulting solution was transferred to the flask containing AgSbF6 via syringe and the mixture stirred for 30 minutes followed by cooling to –78 ℃. Ethyl glyoxylate (1.5 equiv) , the enolsilane from above reaction (1.0 equiv) , and TMS-Cl (2 equiv) were added sequentially and the reaction stirred for 16h at –35 ℃. After the reaction was complete, the mixture was filtered through silica with Et ₂O and the silyl ether was hydrolyzed with 1N HCl in EtOAc (30 min, 25 ℃) to give the hydroxy ester which was purified by flash chromatography. To obtain 44, the following protocol was used. To an oven dried flask was added Me4NHB (OAc) 3 (8.4 equiv) and MeCN/AcOH (1: 1 v/v) to afford a 0.9 M solution which was stirred for 30 min at room temperature before cooling to -20℃. To this mixture, was added a solution of hydroxy-ester (1.0 equiv) in MeCN (0.65 M) and aged for 1 hr at -20℃ before warming to 0℃ and aging for an additional 16 hr. To the reaction was added saturated Rochelle’s salt and saturated NaHCO3 and then extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and washed with NaHCO3 (10 mL) . The aqueous layer was back-extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and concentrated in vacuo to afford a colorless oil which was transferred to a dry flask and charged with benzene (0.23 mL) ,

Synthesis of 45

In a typical procedure (Smietana et al, 2003, Evans et al., 2002) , tetrabutylammonium bromide is heated to 105℃, 2-methyl-3-heptanone (1.0eq) was added, followed by (bistrimethylsilyl) acetamide (BSA) (1.2eq) . The mixture was stirred for 4h at 105℃and directly distilled under reduced pressure without any workup to give the pure silyl enol ether. A dry flask was charged with ScCl3 (thf) 3 (0.15 equiv) and t-Bu-pyridyl-bis (oxazolinyl) ligand (0.17 equiv) in an inert atmosphere (N ₂) glove box. In a separate flask, also in an inert atmosphere (N ₂) glove box, was charged AgSbF6 (0.14 equiv) . Both flasks were brought out of the glove box and the flask containing the metal/ligand was charged with CH ₂Cl ₂ and stirred at room temperature for 1 h. The resulting solution was transferred to the flask containing AgSbF6 via syringe and the mixture stirred for 30 minutes followed by cooling to –78 ℃. Ethyl glyoxylate (1.5 equiv) , the enolsilane from above reaction (1.0 equiv) , and TMS-Cl (2 equiv) were added sequentially and the reaction stirred for 16h at –35℃. After the reaction was complete, the mixture was filtered through silica with Et ₂O and the silyl ether was hydrolyzed with 1N HCl in EtOAc (30 min, 25℃) to give the hydroxy ester which was purified by flash chromatography. To obtain 45, the following protocol was used. To an oven dried flask was added Me4NHB (OAc) 3 (8.4 equiv) and MeCN/AcOH (1: 1 v/v) to afford a 0.9 M solution which was stirred for 30 min at room temperature before cooling to –20℃. To this mixture, was added a solution of hydroxy-ester (1.0 equiv) in MeCN (0.65 M) and aged for 1 hr at –20℃ before warming to 0℃ and aging for an additional 16 hr. To the reaction was added saturated Rochelle’s salt and saturated NaHCO3 and then extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and washed with NaHCO3 (10 mL) . The aqueous layer was back-extracted with CH2Cl2 (4 x 10 mL) . The organic layers were combined and concentrated in vacuo to afford a colorless oil which was transferred to a dry flask and charged with benzene (0.23 mL) ,

Synthesis of 51, 52, 53, 54, 55, 56, 57

In a typical procedure, t-butyl ester hydrochlorides of the respective amino acids (L-Isoleucine t-butyl ester hydrochloride, L-Leucine t-butyl ester hydrochloride, LLtbutyl, IItbutyl, ILtbutyl) were added to t-butyl pantothenate dissolved in DMF, in the presence of EDC (1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide) and HOBt (N-Hydroxybenzotriazole) and stirred at room temperature for 3h to yield the t-butyl esterified versions of the final products. To obtain the final products, the products of the above reaction was dissolved in DCM and TFA was added. The final products 51, 52, 53, 54 and 55 were obtained after purification by column chromatography.

Synthesis of 56, 57

To obtain the tripeptide Leucine-Leucine-Isoleucine-t-butyl ester, Fmoc-L-Leucine was added to L-Leucine-L-Isoleucine-tert-butyl ester (from above) dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature to yield the tripeptide, Fmoc L-Leucine-Leucine-Isoleucine-tert-butyl ester (FmocLLItbutyl) . To obtain the tripeptide, Fmoc L-Isoleucine-Leucine-Isoleucine-t-butyl ester, Fmoc-L-Isoleucine was added to L-Leucine-L-Isoleucine-tert-butyl ester (from above) dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature to yield the tripeptide, Fmoc-L-IsoLeucine-Leucine-Isoleucine-tert-butyl ester (FmocILItbutyl) . To remove the Fmoc groups, piperazine was added to the respective tripeptides to yield L-Leucine-Leucine-Isoleucine-tbutyl ester (LLItbutyl) and L-Isoleucine-Leucine-Isoleucine-tbutyl ester (ILItbutyl) respectively. To obtain 56 and 5-7, the respective tripeptides were added to t-butyl pantothenate dissolved in DMF in the presence of EDC and HOBt and stirred at room temperature for 3h to yield the t-butyl esterified version of 56 and 57. These compounds were subsequently purified and dissolved in DCM and trifluoroacetic acid was added, to yield 56 and 57 respectively.

Synthesis of 58

In a typical procedure (Mondal et al., 2018) , L-Citrulline (1.1 eq) , Fmoc-Cl (1.0 eq) , NaHCO ₃ (2.0 eq) were combined in Dimethylamine/Water (2: 1) at room temperature for 20h, resulting in quantitative yield of Fmoc-L-Citrulline. Subsequently, Fmoc-L-Citrulline was combined with 4-aminobenzyl alcohol (3.0eq) , HATU (1.2eq) and DIPEA (1.0eq) in DMF at room temperature in the dark for 48h. The desired product was then obtained by purification with column chromatography. Subsequently, the Fmoc group was removed via addition of piperazine at room temperature and stirring for 24h. The resulting product was purified via column chromatography. Subsequently, Fmoc-Val-OSu was added to the resulting product dissolved in DMF, and stirred at room temperature for 20h. The resulting product was obtained after purification with column chromatography and the Fmoc group is removed via addition of piperazine. Subsequently, the product is added to pantothenic acid (1.5eq) dissolved in DMF, at room temperature, in the presence of trimethylamine (2.0eq) and N, N'-disuccinimidyl carbonate (1.2 eq) and stirred for 6h. The resultant product was then purified with column chromatography. IL-t-butyl ester (1.0 eq) was combined with triphosgene (2.0 eq) in dichloromethane/NaHCO ₃ (Sat [1: 1] ) at room temperature for 2h and the resultant isocyanate was then added to the above pantothenic-derivatized peptide dissolved in DMF, in the presence of dibutyltin dilaurate (2.0 eq) for 48h and the resultant product, 58, was obtained by purification with column chromatography.

Synthesis of 59

In a typical procedure, Amino-PEG4-t-butyl ester (1.1eq) was added to pantothenic acid dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature for 3h and the product was purified via column chromatography. The product was subsequently dissolved in DCM and trifluoroacetic acid was added to remove the t-butyl group. The resultant product was then purified with column chromatography. The resultant deprotected acid was dissolved in DMF, in the presence of EDC and HOBt and IL-t-butyl (from above, 1.1eq) , was then added. The mixture was stirred at room temperature for 3h and the product was purified via column chromatography. The product was dissolved in DCM and trifluoroacetic acid was added to remove the t-butyl group. The final product, 59, was obtained after purification via column chromatography.

Synthesis of 510

In a typical procedure, cysteamine (1.1eq) was added to pantothenic acid dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature for 3h and the product was purified via column chromatography. 2, 2 dipyridyldisulfide was dissolved in ethanol. The product from the previous reaction was dissolved in DMF and added dropwise to the 2, 2 dipyridyldisulfide solution and stirred at room temperature for 1.5h. The product was then isolated by evaporating the solvent, and then co-evaporating the by-product with anhydrous pyridine. The crude product was then redissolved in ethanol and

-acid (Sigma Aldrich) was dissolved in deionized water and added dropwise to the crude product and stirred at room temperature for 1.5h. The product was then isolated by evaporating the solvent and co-evaporating the by-product with anhydrous pyridine. The final product was then dissolved in DMF, in the presence of EDC and HOBt and IL-t-butyl ester from above was added. The mixture was stirred for 3h and the resulting t-butyl ester was purified via column chromatography. The purified t-butyl ester was then dissolved in DCM and TFA was added subsequently. After 1h, the resultant product 510, was obtained via purification with column chromatography.

Synthesis of 511

In a typical procedure, IL-t-butyl ester is added to Fmoc-Asp (OtBu) -OH (1.5eq) dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature for 3h. The desired Fmoc-protected tripeptide product is obtained via purification with column chromatography. Subsequently, piperazine is added at room temperature to remove the Fmoc group and the product is purified by column chromatography and added to Fmoc-Glu (OtBu) -OH (1.5eq) dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature for 3h. The desired Fmoc-protected tetrapeptide product is obtained via purification with column chromatography. Subsequently, piperazine is added at room temperature to remove the Fmoc group and the product is purified by column chromatography. The deprotected tetrapeptide was subsequently added to pantothenic acid (1.5eq) dissolved in DMF, in the presence of EDC and HOBt and stirred at room temperature for 3h. The resultant product was obtained by column chromatography and redissolved in DCM and TFA was added and the mixture was stirred for an hour, the resultant product, 511, was obtained by column chromatography.

EXAMPLE 2

In order to test if our compounds (21, 22, 23, 24, 25, 26, 27, 28, 29, 210, 211, 22L, 22I, 211L, 211I, 31, 32, 33, 34, 35, 36, 37, 38, 39, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 41, 42, 43, 44, 45, 46, 47, 48, 49, 410, 411, 412, 51, 52, 53, 54, 55, 56, 57, 58, 59, 510, 511, 512) can promote tissuegenesis, tissue growth, and prevent the deaths. weight loss and tissue senescence of aged mice, we performed experiments on inflammaging mouse models. As exemplified below, we found that all the compounds with the exception of 24, 25, 26, 28, 29, can promote tissuegenesis and prevent the tissue senescence of inflammaging mice, as observed from decreases in death rates, body weight loss, limb tissue loss, tissue degeneration, cellular damage, fibrosis, inflammation and senescence, and restoration of muscle stem cell-mediated tissue growth, tissue repair, tissue regeneration, proliferation, differentiation, and physical endurance and overall strength, after bleomycin-induction of lung disease, cytokine inflammatory storms, sarcopenia and cachexia. FIG. 1 shows the schematic for modeling inflammaging in vivo, by using bleomycin (3mg/kg in 50ul PBS, intratracheal) to induce chronic obstructive pulmonary disease (COPD) , cytokine release syndrome (CRS) , sarcopenia and cachexia. FIG. 2 shows the Kaplan-Meier survival curves for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly increased survival and prevented death, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment (*P<0.05) . FIG. 3 shows the total body weight (%of initial weight) changes for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly prevented body weight loss (*P<0.05) , compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. FIG. 4 shows the limb tissue mass (grams) for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly prevented loss of tissue mass and promoted tissuegenesis, tissue growth and tissue repair (*P<0.05) , compared to leucine (L) alone, or DMSO vehicle treatment. FIG. 5 shows the serum lactate dehydrogenase (LDH) levels for inflammaging mice. The results show that all the compounds with the exception of 24, 25, 26, 28, 29 significantly reduced cellular damage, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment (*P<0.05) . FIG. 6 shows the quantification of new Myh3+ myofibers that incorporated muscle stem cells (BrdU+) . The results show that all the compounds with the exception of 24, 25, 26, 28, 29, enhance tissue regeneration via higher proliferation, differentiation and fusion of BrdU+ muscle stem cells with new myofibers, compared to leucine (L) alone, isoleucine (I) alone or DMSO vehicle treatment (**P<0.01) . Furthermore the serum TNFa levels for inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced inflammation, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the serum IL-6 levels for inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced inflammation, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the serum IL-8 levels for inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced inflammation, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the serum IL-1b levels for inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced inflammaging, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the %proportion of senescent cells in the lungs of inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced senescence in the lung, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the %proportion of fibrotic cells in the lungs of inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced fibrosis in the lung, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the %proportion of inflammatory cells in the lungs of inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced inflammaging in the lung, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the %proportion of senescent cells in the quadriceps muscles of inflammaging mice show that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced senescence in the muscles, compared to leucine (L) alone, isoleucine (I) alone, or DMSO vehicle treatment. Furthermore the treadmill test showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the physical endurance (running distance) of the inflammaging mice, compared to DMSO vehicle treatment and wildtype mice. Furthermore the forelimb grip test showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the physical strength of the inflammaging mice, compared to DMSO vehicle treatment and wildtype mice. Furthermore histopathology showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the muscle fiber cross-sectional area (CSA) of the inflammaging mice, compared to DMSO vehicle treatment and wildtype mice. Furthermore DEXA scans showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the bone mineral density of the inflammaging mice, compared to DMSO vehicle treatment and wildtype mice. Furthermore the treadmill test showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the physical endurance (running distance) of the aged mice, compared to DMSO vehicle treatment and young mice. Furthermore the forelimb grip test showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the physical strength of aged mice, compared to DMSO vehicle treatment and young mice. Furthermore histopathology showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the muscle fiber cross-sectional area (CSA) of aged mice, compared to DMSO vehicle treatment and young mice. Furthermore DEXA scans showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly restored the bone mineral density of aged mice, compared to DMSO vehicle treatment and young mice.

Furthermore, frailty index score calculations showed that all the compounds with the exception of 24, 25, 26, 28, 29, significantly reduced frailty, compared to leucine (L) alone, isolecuine (I) alone, or DMSO vehicle treatment.

EXAMPLE 3

We further explored the use of the calcium salt of 22 (abbreviated as 22 henceforth and in FIG 7-24 and corresponding figure legends for convenience) in combination with varying concentration of amino acids in treating cachexia, fibrosis and metabaging diseases (subcutaneous 3mg/kg bleomycin in 50ul PBS) . After inducing cachexia in the mouse models for 4 days, varying amounts of 22 and leucine, namely 20mg/kg of 22 (22 only) , 20mg/kg of leucine (Leucine only) , 20mg/kg of 22+20mg/kg of leucine (22+leucine (high) ) and 20mg/kg of 22+10mg/kg of leucine (22+leucine (low) ) were added to different groups of 10 mice each and based on the results as demonstrated in FIG7, we are able to restore weight in cachexia, whereas the vehicle control (ctr) could not. We further examined the muscle cells and tissues in the above mice and found that adding 20mg/kg of 22+10mg/kg of leucine (22+leu) increased muscle stem cell proliferation and growth (ki67+ cells and Pax7+) (FIG8) and increased the cross sectional area (CSA) and Feret diameter of myofibers (FIG9) in mice more than when 20ng/kg of 22 (22 or 22 only) or 20mg/kg leucine (leucine or leu) alone was added. Next, we did western blots on the mice muscles and found that the combination of 20mg/kg of 22 and 10mg/kg of leucine (22+leu) induces synergistic phosphorylation of ribosomal S6 protein (Cell Signaling antibody) , a 32kDa protein that is also a marker of mTOR activation. As a result, 22+leu also induced a synergistic restoration of myosin heavy chain (MHC) protein (Sigma Aldrich antibody) , a marker of myogenesis and muscle growth. In contrast, the vehicle control (ctrl) , 22 alone, and leucine (leu) alone, were not as effective in inducing mTOR activation and muscle growth. The results are demonstrated in FIG 10. We analyzed the lung tissue section of the vehicle control-treated cachexia mice and cachexia mice treated with 20mg/kg of 22 and 10mg/kg of leucine with Masson Trichome staining (where the blue areas represent fibrosis) , extracted the blue channel with ImageJ (NIH) and quantified the blue channel accordingly after normalizing against the area of the lung tissue section. As demonstrated in FIG 11, lung sections of the vehicle control-treated mice demonstrated a greater extent of fibrosis area compared to the treated group, demonstrating that treatment with 20mg/kg of 22 and 10mg/kg of leucine is able to reverse or ameliorate fibrosis. As demonstrated in FIG 12, hematoxylin and eosin (H&E) staining further showed that lung sections of the vehicle control-treated mice demonstrated a higher grade of inflammation compared to the treated group, demonstrating that treatment with 20mg/kg of 22 and 10mg/kg of leucine is able to ameliorate inflammaging. We then performed forelimb grip tests, and found that treatment with 20mg/kg of 22 and 10mg/kg of leucine is able to significantly restore the physical strength of the cachexia mice, as shown in FIG 13. We further performed clinical hematology studies on vehicle control-treated cachexia mice, cachexia mice treated with 20mg/kg of 22 and 10mg/kg of leucine (22+L) , and normal mice, and found that 22+L decreased inflammatory neutrophils (Neu) back to normal levels, and restored lymphocytes (Lym) , monocytes (Mono) and eosinophils (Eos) back to higher normal levels. Some of these data is demonstrated in FIG 14. We also saw restoration of platelet levels back to higher normal level in in cachexia mice treated with 22+L in comparison with the vehicle control mice in FIG 15. We also analyzed the blood chemistry of vehicle control-treated cachexia mice (Control) , cachexia mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) , 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) respectively and the results are demonstrated in FIG 16, 17 and Fig 18. FIG 16 demonstrates the uric acid levels in vehicle control-treated cachexia mice (Control) , cachexia mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) , 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) respectively. Uric acid (UA) , the end-product of purine metabolism, is elevated in cachexia due to tissue wasting and upregulated xanthine oxidase (XO) activity. FIG 17 demonstrates creatinine levels in vehicle control-treated cachexia mice (Control) , cachexia mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) , 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) respectively. Creatinine is a biomarker of muscle mass. Currently, 24 h creatinine excretion rate is used as a measure of muscle wasting, and recent studies have shown that lower urinary creatinine is an independent predictor of worse outcomes in the general population and in various chronic illnesses such as chronic heart failure, coronary artery disease, cardiomyopathies, diabetes mellitus, etc ( https: //onlinelibrary. wiley. com/doi/full/10.1002/jcsm. 12690, https: //www. ncbi. nlm. nih. gov/pmc/articles/PMC4842835/) . FIG 18 demonstrates low density lipoprotein (LDL) levels in vehicle control-treated cachexia mice (Control) , cachexia mice treated with 20mg/kg of 22 (22) , 20mg/kg of leucine (Leu) , 20mg/kg of 22 and 20mg/kg of leucine (22L (hi) ) , 20mg/kg of 22 and 10mg/kg of leucine (22L (lo) ) respectively. LDL causes muscle wasting and is known to be associated with inflammaging and the associated metabaging and steatohepatitis ( https: //www. ncbi. nlm. nih. gov/pmc/articles/PMC5794421/) . Therefore, these results further show that 22L (lo) is able to treat and counter metabaging diseases in affected tissues/organs.

EXAMPLE 4

Physiological muscle disuse atrophy can arise in bedridden (aged) patients or patients with neuromuscular injury. To model physiological muscle disuse atrophy, sciatic nerve transection was performed on mice to induce muscle denervation and loss of muscle activity. As previously reported, the muscle mass of the hindlimb extensor digitorum longus (EDL, fast-twitch) , soleus (SOL, slow-twitch) , and gastrocnemius (mixed fiber) all decreased rapidly upon denervation. This can be ascertained by simply measuring the thigh maximum circumference, or by measuring the myosin heavy chain (MHC) content and myofiber diameters within the hindlimb after 2 to 3 weeks. In general, all skeletal muscle subtypes atrophied rapidly after denervation or disuse. In our experiments, ten week old male C57BL/6 J mice, housed in a day–night cycle of 24 h, were subjected to denervation in the left hindlimb by tibial nerve transection. Briefly, mice in the denervation groups were anesthetized using isoflurane, and a 3-mm piece of the tibial nerve was removed. The sham mice underwent the same procedure without removal of the tibial nerve piece. The mice were then randomly divided into four groups (6 mice/group) : sham-operation group (control) , denervation group, sham + 22+L (20 mg/kg of 22 +10 mg/kg of Leucine) group, denervation + 22+L (20 mg/kg of 22 +10 mg/kg of Leucine) group, for experimentation and caution. Mice in the sham group underwent the same surgery as the mice in the denervated groups, but the tibial nerve was not transected. Our results (FIG. 19) showed that the thigh circumference of the sham group was generally stable after surgery, whereas the thigh circumference of the denervation group declined steadily within 20 days after surgery. When 22+L was injected subcutaneously daily, it had little effect on the sham group, but induced a remarkable recovery in the thigh circumference of the denervated group between day 14 and day 24. If we plot the average difference in thigh circumference between the sham and denervated groups over time, the recovery induced by 22+L injection, relative to PBS vehicle control injection, becomes even clearer (FIG. 20) When we measured the hanging time of the mice, as a surrogate measure of the mouse strength and endurance, we found that 22+L injection dramatically increased mouse strength and endurance, relative to PBS vehicle control injection (FIG. 21) . Given that 22+L administered subcutaneously was effective, it is therefore very likely topical or transdermal administration of 22+L may be effective as well.

EXAMPLE 5

Cirrhosis is an example of a late stage liver disease caused by many forms of liver diseases and conditions, such as viral infection, hepatitis, fatty liver disease, non-alcoholic steatohepatitis (NASH) and chronic alcoholism. Each time the liver is injured -whether by infection, disease, excessive alcohol consumption or another cause, it tries to repair itself. In the process, scar tissue forms. Thus, cirrhosis is a slowly developing disease in which healthy liver tissue and bile ducts are replaced with scar tissue. The scar tissue blocks the flow of blood through the liver and slows the liver capacity to process nutrients, hormones, drugs and natural toxins (poisons) . It also reduces the production of proteins, lipoproteins and other substances such as cholesterol, which are usually made in the liver. Late-stage cirrhosis is life-threatening. Scientists estimate that cirrhosis of the liver affects about one in 400 adults in the U.S. It affects about 1 in 200 adults age 45 to 54, the age group most commonly affected by cirrhosis. Cirrhosis causes about 26,000 deaths each year in the U.S. and is the seventh leading cause of death in the U.S. among adults 25 to 64 years of age. We used genotoxins to induce and model cirrhosis in eight weeks old male C57BL/6J mice for 2 weeks (single dose of intraperitoneal 90 mg/kg diethylnitrosamine or 3mg/kg bleomycin) . The mice were randomly divided into two groups (4 mice/group) : vehicle control group (control) , and the 22+L (20 mg/kg of 22 +10 mg/kg of Leucine, treated) group. Both groups received subcutaneous injections of vehicle or 22+L daily. These mice were also compared to a normal age matched littermate mouse. At the end of 2 weeks, the mice were sacrificed for clinical blood chemistry. The results in FIG. 22 showed that the control mice plasma had dramatically higher levels of the liver cirrhosis markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the normal mouse, whereas the treated mice had significantly lower levels of the liver cirrhosis markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver cirrhosis. The results in FIG. 23 showed that the control mice plasma had higher levels of the biliary cirrhosis markers direct bilirubin (DBIL) and total bilirubin (TBIL) than the normal mouse, whereas the treated mice had significantly lower levels of the biliary cirrhosis markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver biliary cirrhosis. The results in FIG. 24 showed that the control mice plasma had dramatically lower levels of the liver biosynthetic function markers cholesterol (CHOL) , HDLc (high density lipoprotein cholesterol) and LDLc (low density lipoprotein cholesterol) , than the normal mouse, as is indicative of cirrhotic hypocholesterolemia and chronic hepatic insufficiency (see DOI: 10.1080/00365529850172593) , whereas the treated mice had significantly higher and near-normal levels of these liver biosynthetic function markers (*P<0.05) , indicating that the 22+L treatment ameliorated liver cirrhosis. Given that 22+L administered subcutaneously was effective, it is therefore very likely topical or transdermal administration of 22+L may be effective as well.

Claims

A composition of matter for weight management, that comprises compound B, a salt, solvate, tautomer, analog, or stereoisomer thereof, where B can be represented by any one of the formulas or chemical structures chosen from any one of the following formulas or chemical structures or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to promote weight gain that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to promote limb or muscle mass gain that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formulas or chemical structures or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to prevent or treat involuntary weight loss that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to prevent or treat uncontrolled involuntary weight loss that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to enable weight restoration that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to promote physical endurance that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to relieve sports fatigue that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter to replenish nutrition to promote tissue health that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that promotes growth or repair of a tissue, that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that induces differentiation and/or maturation of progenitors in a tissue, compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures, chosen from any of the following formula or chemical structure or combinations thereof:
Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that induces proliferation of stem cells or progenitor cells in a tissue, compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that increases expression of proliferation biomarkers (e.g ki67+ or BrdU+) in a tissue, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that increases tissue mass in an individual, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that promotes tissuegenesis, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that prevents or treats fibrosis, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that prevents or treat aging, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that prevents or treats inflammaging, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that prevents or treats senescence, comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A composition of matter that prevents or treats frailty, that comprises compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, where B can be represented by any of the formulas or chemical structures chosen from any of the following formula or chemical structure or combinations thereof:

Where R is a hydrocarbon, that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and V and G comprises of any number of carbon, hydrogen, oxygen, phosphorus, sulphur, and/or nitrogen atoms.

Where R ₃ can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, hydroxyl, amino, sulphydryl, fluoro, chloro, bromo, iodo, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group.
A method of administering the composition of matter in any one of claims 1-20 to an individual, wherein the tissue is from an aged individual.
The composition of matter in any of one of the claims 1 to 21, wherein compound B can be further represented by any of following formulas or chemical structures or combinations thereof:

Where R ₁ is a hydrocarbon that can be selected from but not limited to: alkyl, aryl, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloaryl, heteroalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, heteroaryl and heteroarylalkyl, alkoxy, polyethylene glycol group and X can be selected from any of the following: COOH, OH, SH, NH ₂, amide, esters, phosphate, phosphonate, sulphate, nitro, heteroalkyl, heteroaryl, heteroalkenyl, heteroalkynyl.

Where V ₁ consists of any amount of carbon, hydrogen, phosphorus, sulphur, oxygen, or nitrogen atoms and V ₂ is a hydrogen or a hydrocarbon (i.e CH ₃) group and can be chosen but not limited to any of the following groups: acetyl, carboxyl, carbamate, phosphoester, phosphodiester, phosphoramidite, phosphoramidic acid, phosphoramide, ethylene glycol, sugar moiety and/or glycol.

Where L can be a hydrolysable linker, branched or linear and may include functional handles such as -O-, -S-, -NR-, - (C=O) -, -SO-, -SO ₂, phosphodiester, maleimide, N-hydroxy-succinimide esters, amines, and carboxylic acids, for conjugation, modification, and crosslinking orL does not exist and Z is directly linked to the rest of the molecule in the form of an amide linkage. And Z is an amino acid or a peptide, wherein, the amino acid can be either leucine or isoleucine and the peptide consists of at least one or several units of leucine or/and isoleucine.
The composition of matter in any one of claims 1-22, wherein compound B is 4-Phosphopantothenate, 4-Phosphopantothenoylcysteine, 4-Phosphopantetheine, Dephospho-Coenzyme A, Coenzyme A or can represented by the formula or chemical structure (2) in Claim 22, where R ₁ and X are further defined in the table below.
The composition of matter in any one of claims 1-22, wherein compound B can represented by the formula or chemical structure (3) in Claim 22, where V ₁ and V ₂ are further defined in the tables below.
The composition of matter in any one of claims 1-22, wherein compound B is can represented by the formula or chemical structure (4) in Claim 22, where R ₃ is further defined in the table below.
The composition of matter in any one of claims 1-22, wherein compound B is can represented by the formula or chemical structure (5) in Claim 22, where L and Z are further defined in the table below.
The composition of matter in any one of claims 1-23, wherein compound B is can represented by the formula or chemical structure 22 in Claim 23.
A method of administering the composition of matter in any of claims 1-23, comprising administering a composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof in the form of a nutritional supplement, a dietary supplement or a nutraceutical composition.
A method of administering the composition of matter in any of claims 1-23, comprising administering a composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof in the form of a cosmetic product or cosmeceutical composition.
The method of claim 28 or 29, wherein the composition of matter in any of claims 1-23, can be ingested, injected or adsorbed through the skin.
A method of treating a disease or condition in an individual, comprising administering an effective amount of a pharmaceutical composition comprising compound B, a salt, solvate, tautomer, analog or stereoisomer thereof to the individual.
The method of any one of claims 1-31, wherein the disease or condition is injury or aging.
The method of any one of claims 1-32, wherein the disease or condition is tissue degeneration or fibrosis.
The method of any one of claims 1-32, wherein the disease or condition is aging.
The method of any one of claims 1-35, wherein the disease or condition is selected from the group consisting of sarcopenia, cachexia, disuse atrophy, myopathies, alopecia cardiomyopathies, chronic heart failure, chronic kidney failure, skin wrinkling, balding, macular degeneration, fatty liver disease, liver steatosis, steatohepatitis, type 2 diabetes (T2D) , chronic obstructive pulmonary disease (COPD) , osteoarthritis, osteoporosis, fibrosis, Alzheimer’s Disease, Parkinson’s Disease, dementia, atherosclerosis, cardiovascular disease, arthritis, rheumatoid arthritis, periodontitis, cataracts, osteoporosis, fibrosis, cirrhosis, chronic hepatic insufficiency, idiopathic pulmonary fibrosis, cardiac fibrosis, uterine fibrosis, scarring, arthrofibrosis, chronic kidney disease, Crohn’s disease, keloids, myelofibrosis, retroperitoneal fibrosis, scleroderma, sclerosis, chronic wounds (such as diabetic foot ulcer) , chronic dermal fibrosis, cutaneous fibrosis, skin aging, nonalcoholic steatohepatitis (NASH) , hair loss, tissue atrophy, menopause, ovarian aging, primary ovarian insufficiency, endometrial hyperplasia, adenomyosis and sarcopenia, neurodegenerative diseases and any other disease resulting from injury, surgery, cancer, congenital, developmental, and environmental loss or damage to tissue
The method of claim 1-36, wherein the composition is administered via any of the following routes or combinations thereof: oral, rectal, nasal, topical (including buccal and sublingual) , transdermal, vaginal, parenteral (including intramuscular, subcutaneous and intravenous) , inhalation, intratracheal, intravenous, intraarterial, intracoronary, intrathecal, intraperitoneal, intramyocardial, trans-endocardial, trans-epicardial, subcutaneous, topical, transdermal, or otic
The method of any one of claims 1-37, wherein the composition comprises in addition to compound B, a salt, solvate, tautomer, analog or stereoisomer thereof, amino acids, peptides or combinations thereof.
The method of any one of claims 1-38, wherein the amino acids comprise of isoleucine, leucine or combinations thereof.
The method of any one of claims 1-38, wherein the peptides comprise of one or multiple units of isoleucine, leucine or combinations thereof.
The method of any one of claims 1-40, wherein the peptides or amino acids are administered in the form of a protein supplement or protein source such as but not limited to whey proteins, soy proteins, insect proteins, egg proteins, vegan proteins, plant-based proteins, animal proteins, microbial proteins, synthetic proteins, meat, plant-based meat, milk, plant-based milk, artificial milk, plant-based egg, synthetic egg, meat products, plant-based meat products, synthetic meat products, dairy products, artificial dairy products, plant-based dairy products.