HRP20050461A2 - Soluble notch-based substrates for gamma secretase and methods and compositions for using same - Google Patents

Soluble notch-based substrates for gamma secretase and methods and compositions for using same Download PDF

Info

Publication number: HRP20050461A2
Authority: HR; Croatia
Prior art keywords: notch; secretase; protein; cleavage; fusion protein
Prior art date: 2002-11-26

Application number

HR20050461A

Other languages

English (en)

Croatian (hr)

Inventor

Bruce Rank Kenneth

Kumar Sharma Satish

Original Assignee

Pharmacia & Upjohn Company Llc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-11-26

Filing date

2005-05-24

Publication date

2005-08-31

2005-05-24 Application filed by Pharmacia & Upjohn Company Llc filed Critical Pharmacia & Upjohn Company Llc

2005-08-31 Publication of HRP20050461A2 publication Critical patent/HRP20050461A2/hr

Links

102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title claims description 189
108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title claims description 188
238000000034 method Methods 0.000 title claims description 95
239000000758 substrate Substances 0.000 title claims description 81
239000000203 mixture Substances 0.000 title description 17
102000005650 Notch Receptors Human genes 0.000 claims description 193
108010070047 Notch Receptors Proteins 0.000 claims description 193
238000003776 cleavage reaction Methods 0.000 claims description 159
230000007017 scission Effects 0.000 claims description 147
102000037865 fusion proteins Human genes 0.000 claims description 124
108020001507 fusion proteins Proteins 0.000 claims description 124
108090000623 proteins and genes Proteins 0.000 claims description 115
108090000765 processed proteins & peptides Proteins 0.000 claims description 114
150000001875 compounds Chemical class 0.000 claims description 92
102000004169 proteins and genes Human genes 0.000 claims description 89
102000004196 processed proteins & peptides Human genes 0.000 claims description 76
229920001184 polypeptide Polymers 0.000 claims description 63
241001195348 Nusa Species 0.000 claims description 40
238000003556 assay Methods 0.000 claims description 40
150000001413 amino acids Chemical class 0.000 claims description 27
238000012545 processing Methods 0.000 claims description 25
238000012360 testing method Methods 0.000 claims description 20
230000001404 mediated effect Effects 0.000 claims description 19
239000012634 fragment Substances 0.000 claims description 18
238000000338 in vitro Methods 0.000 claims description 14
102000040430 polynucleotide Human genes 0.000 claims description 12
108091033319 polynucleotide Proteins 0.000 claims description 12
239000002157 polynucleotide Substances 0.000 claims description 12
239000002773 nucleotide Substances 0.000 claims description 10
125000003729 nucleotide group Chemical group 0.000 claims description 10
230000007026 protein scission Effects 0.000 claims description 8
238000005259 measurement Methods 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 5
239000007864 aqueous solution Substances 0.000 claims description 4
241000251539 Vertebrata <Metazoa> Species 0.000 claims description 2
101710137189 Amyloid-beta A4 protein Proteins 0.000 claims 4
101710151993 Amyloid-beta precursor protein Proteins 0.000 claims 4
102100022704 Amyloid-beta precursor protein Human genes 0.000 claims 4
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims 4
229940124639 Selective inhibitor Drugs 0.000 claims 2
210000004027 cell Anatomy 0.000 description 79
230000000694 effects Effects 0.000 description 54
230000014509 gene expression Effects 0.000 description 53
238000002360 preparation method Methods 0.000 description 41
230000004927 fusion Effects 0.000 description 34
239000013598 vector Substances 0.000 description 28
239000003795 chemical substances by application Substances 0.000 description 27
239000012528 membrane Substances 0.000 description 24
238000000746 purification Methods 0.000 description 24
102000004190 Enzymes Human genes 0.000 description 22
108090000790 Enzymes Proteins 0.000 description 22
229940088598 enzyme Drugs 0.000 description 22
239000013604 expression vector Substances 0.000 description 20
238000002965 ELISA Methods 0.000 description 19
241000588724 Escherichia coli Species 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
239000003112 inhibitor Substances 0.000 description 17
108020004414 DNA Proteins 0.000 description 16
230000005764 inhibitory process Effects 0.000 description 16
239000003814 drug Substances 0.000 description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
239000000047 product Substances 0.000 description 15
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
241000282414 Homo sapiens Species 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
239000000872 buffer Substances 0.000 description 14
102000039446 nucleic acids Human genes 0.000 description 14
108020004707 nucleic acids Proteins 0.000 description 14
150000007523 nucleic acids Chemical class 0.000 description 14
241001465754 Metazoa Species 0.000 description 13
240000004808 Saccharomyces cerevisiae Species 0.000 description 13
210000004962 mammalian cell Anatomy 0.000 description 13
239000000243 solution Substances 0.000 description 13
102000005720 Glutathione transferase Human genes 0.000 description 12
108010070675 Glutathione transferase Proteins 0.000 description 12
108091028043 Nucleic acid sequence Proteins 0.000 description 12
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 12
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 12
210000004899 c-terminal region Anatomy 0.000 description 12
208000024827 Alzheimer disease Diseases 0.000 description 11
108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 description 11
102100023181 Neurogenic locus notch homolog protein 1 Human genes 0.000 description 11
239000003550 marker Substances 0.000 description 11
230000001105 regulatory effect Effects 0.000 description 11
238000013518 transcription Methods 0.000 description 11
230000035897 transcription Effects 0.000 description 11
229920001213 Polysorbate 20 Polymers 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
238000001514 detection method Methods 0.000 description 10
239000003623 enhancer Substances 0.000 description 10
238000002875 fluorescence polarization Methods 0.000 description 10
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 10
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 10
241000894006 Bacteria Species 0.000 description 9
DWJXYEABWRJFSP-XOBRGWDASA-N DAPT Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)OC(C)(C)C)C=1C=CC=CC=1)C(=O)CC1=CC(F)=CC(F)=C1 DWJXYEABWRJFSP-XOBRGWDASA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 9
101800001628 Notch 1 intracellular domain Proteins 0.000 description 9
102400000552 Notch 1 intracellular domain Human genes 0.000 description 9
238000011977 dual antiplatelet therapy Methods 0.000 description 9
238000005516 engineering process Methods 0.000 description 9
239000003540 gamma secretase inhibitor Substances 0.000 description 9
239000013612 plasmid Substances 0.000 description 9
230000008569 process Effects 0.000 description 9
230000003612 virological effect Effects 0.000 description 9
108010036933 Presenilin-1 Proteins 0.000 description 8
102000012412 Presenilin-1 Human genes 0.000 description 8
238000001597 immobilized metal affinity chromatography Methods 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
238000004519 manufacturing process Methods 0.000 description 8
239000002609 medium Substances 0.000 description 8
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 7
102000001759 Notch1 Receptor Human genes 0.000 description 7
108010029755 Notch1 Receptor Proteins 0.000 description 7
238000007792 addition Methods 0.000 description 7
230000001419 dependent effect Effects 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000000499 gel Substances 0.000 description 7
230000003993 interaction Effects 0.000 description 7
108020004999 messenger RNA Proteins 0.000 description 7
239000000825 pharmaceutical preparation Substances 0.000 description 7
150000003839 salts Chemical class 0.000 description 7
238000002741 site-directed mutagenesis Methods 0.000 description 7
239000000126 substance Substances 0.000 description 7
238000001262 western blot Methods 0.000 description 7
238000004458 analytical method Methods 0.000 description 6
230000001580 bacterial effect Effects 0.000 description 6
230000027455 binding Effects 0.000 description 6
230000001413 cellular effect Effects 0.000 description 6
238000005119 centrifugation Methods 0.000 description 6
230000002255 enzymatic effect Effects 0.000 description 6
230000006870 function Effects 0.000 description 6
230000012010 growth Effects 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
230000035772 mutation Effects 0.000 description 6
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
239000007787 solid Substances 0.000 description 6
230000014616 translation Effects 0.000 description 6
241000699666 Mus <mouse, genus> Species 0.000 description 5
108091034117 Oligonucleotide Proteins 0.000 description 5
239000007983 Tris buffer Substances 0.000 description 5
239000003242 anti bacterial agent Substances 0.000 description 5
238000010367 cloning Methods 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
235000011187 glycerol Nutrition 0.000 description 5
238000011534 incubation Methods 0.000 description 5
230000000977 initiatory effect Effects 0.000 description 5
239000003446 ligand Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
244000005700 microbiome Species 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
230000010287 polarization Effects 0.000 description 5
230000008488 polyadenylation Effects 0.000 description 5
230000002797 proteolythic effect Effects 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
230000002103 transcriptional effect Effects 0.000 description 5
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
241000701022 Cytomegalovirus Species 0.000 description 4
241000196324 Embryophyta Species 0.000 description 4
229940125373 Gamma-Secretase Inhibitor Drugs 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
108700026244 Open Reading Frames Proteins 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
108700008625 Reporter Genes Proteins 0.000 description 4
241000700605 Viruses Species 0.000 description 4
238000010171 animal model Methods 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000003599 detergent Substances 0.000 description 4
238000009510 drug design Methods 0.000 description 4
238000001962 electrophoresis Methods 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000000284 extract Substances 0.000 description 4
102000038383 gamma-secretases Human genes 0.000 description 4
108091007739 gamma-secretases Proteins 0.000 description 4
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
238000000099 in vitro assay Methods 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
238000010647 peptide synthesis reaction Methods 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000001742 protein purification Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
230000028327 secretion Effects 0.000 description 4
238000000926 separation method Methods 0.000 description 4
150000003384 small molecules Chemical class 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
238000013519 translation Methods 0.000 description 4
229940124648 γ-Secretase Modulator Drugs 0.000 description 4
VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical group C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 description 3
GUQQBLRVXOUDTN-XOHPMCGNSA-N 3-[dimethyl-[3-[[(4r)-4-[(3r,5s,7r,8r,9s,10s,12s,13r,14s,17r)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]propyl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CC(O)CS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 GUQQBLRVXOUDTN-XOHPMCGNSA-N 0.000 description 3
108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
102000053602 DNA Human genes 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
241000238631 Hexapoda Species 0.000 description 3
241000282412 Homo Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
108060001084 Luciferase Proteins 0.000 description 3
239000005089 Luciferase Substances 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
101710182846 Polyhedrin Proteins 0.000 description 3
102000012419 Presenilin-2 Human genes 0.000 description 3
108010036908 Presenilin-2 Proteins 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
241000256251 Spodoptera frugiperda Species 0.000 description 3
102000006601 Thymidine Kinase Human genes 0.000 description 3
108020004440 Thymidine kinase Proteins 0.000 description 3
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
230000009471 action Effects 0.000 description 3
238000001042 affinity chromatography Methods 0.000 description 3
108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 3
230000000844 anti-bacterial effect Effects 0.000 description 3
229940121375 antifungal agent Drugs 0.000 description 3
239000003429 antifungal agent Substances 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
230000005754 cellular signaling Effects 0.000 description 3
230000008859 change Effects 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
239000000470 constituent Substances 0.000 description 3
238000011161 development Methods 0.000 description 3
230000018109 developmental process Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
239000002612 dispersion medium Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
238000007876 drug discovery Methods 0.000 description 3
238000011156 evaluation Methods 0.000 description 3
230000002068 genetic effect Effects 0.000 description 3
238000013537 high throughput screening Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
230000001939 inductive effect Effects 0.000 description 3
239000006166 lysate Substances 0.000 description 3
229910021645 metal ion Inorganic materials 0.000 description 3
238000012544 monitoring process Methods 0.000 description 3
239000008177 pharmaceutical agent Substances 0.000 description 3
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
230000002265 prevention Effects 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000003259 recombinant expression Methods 0.000 description 3
230000010076 replication Effects 0.000 description 3
238000007423 screening assay Methods 0.000 description 3
230000011664 signaling Effects 0.000 description 3
239000000606 toothpaste Substances 0.000 description 3
VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 2
108010025188 Alcohol oxidase Proteins 0.000 description 2
102000002260 Alkaline Phosphatase Human genes 0.000 description 2
108020004774 Alkaline Phosphatase Proteins 0.000 description 2
108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
241000272517 Anseriformes Species 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
102000011727 Caspases Human genes 0.000 description 2
108010076667 Caspases Proteins 0.000 description 2
241000701489 Cauliflower mosaic virus Species 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
101100127285 Drosophila melanogaster unc-104 gene Proteins 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
238000012286 ELISA Assay Methods 0.000 description 2
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
241000233866 Fungi Species 0.000 description 2
108091027305 Heteroduplex Proteins 0.000 description 2
241000701024 Human betaherpesvirus 5 Species 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
241000713333 Mouse mammary tumor virus Species 0.000 description 2
101100294417 Mus musculus Notch1 gene Proteins 0.000 description 2
229930193140 Neomycin Natural products 0.000 description 2
241000235648 Pichia Species 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
230000006819 RNA synthesis Effects 0.000 description 2
102100030000 Recombining binding protein suppressor of hairless Human genes 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
108700026226 TATA Box Proteins 0.000 description 2
108090000190 Thrombin Proteins 0.000 description 2
241000723873 Tobacco mosaic virus Species 0.000 description 2
108700019146 Transgenes Proteins 0.000 description 2
241000255985 Trichoplusia Species 0.000 description 2
108090000848 Ubiquitin Proteins 0.000 description 2
102000044159 Ubiquitin Human genes 0.000 description 2
241000269370 Xenopus <genus> Species 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
239000013543 active substance Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
102000005936 beta-Galactosidase Human genes 0.000 description 2
108010005774 beta-Galactosidase Proteins 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
229960002685 biotin Drugs 0.000 description 2
235000020958 biotin Nutrition 0.000 description 2
239000011616 biotin Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
229910021538 borax Inorganic materials 0.000 description 2
210000004900 c-terminal fragment Anatomy 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000004671 cell-free system Anatomy 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
230000002860 competitive effect Effects 0.000 description 2
238000010276 construction Methods 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
230000002939 deleterious effect Effects 0.000 description 2
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
239000007850 fluorescent dye Substances 0.000 description 2
238000005194 fractionation Methods 0.000 description 2
230000030279 gene silencing Effects 0.000 description 2
230000013595 glycosylation Effects 0.000 description 2
238000006206 glycosylation reaction Methods 0.000 description 2
239000005090 green fluorescent protein Substances 0.000 description 2
239000005556 hormone Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
210000005260 human cell Anatomy 0.000 description 2
230000006698 induction Effects 0.000 description 2
238000003780 insertion Methods 0.000 description 2
230000037431 insertion Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
230000006662 intracellular pathway Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
238000001155 isoelectric focusing Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
239000007951 isotonicity adjuster Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
230000003278 mimic effect Effects 0.000 description 2
239000002324 mouth wash Substances 0.000 description 2
229940051866 mouthwash Drugs 0.000 description 2
238000002703 mutagenesis Methods 0.000 description 2
231100000350 mutagenesis Toxicity 0.000 description 2
229930014626 natural product Natural products 0.000 description 2
229960004927 neomycin Drugs 0.000 description 2
210000002682 neurofibrillary tangle Anatomy 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
230000008520 organization Effects 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
235000020030 perry Nutrition 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
235000011007 phosphoric acid Nutrition 0.000 description 2
230000001323 posttranslational effect Effects 0.000 description 2
230000000750 progressive effect Effects 0.000 description 2
238000000159 protein binding assay Methods 0.000 description 2
238000001243 protein synthesis Methods 0.000 description 2
RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
238000012552 review Methods 0.000 description 2
238000003118 sandwich ELISA Methods 0.000 description 2
239000013605 shuttle vector Substances 0.000 description 2
235000010339 sodium tetraborate Nutrition 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
238000003860 storage Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
102000013498 tau Proteins Human genes 0.000 description 2
108010026424 tau Proteins Proteins 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
229960004072 thrombin Drugs 0.000 description 2
229940034610 toothpaste Drugs 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 2
241000701447 unidentified baculovirus Species 0.000 description 2
MEYZIGGCNFHINA-UHFFFAOYSA-N (6-aminoquinolin-2-yl) n-(2,5-dioxopyrrolidin-1-yl)-n-hydroxycarbamate Chemical compound C1=CC2=CC(N)=CC=C2N=C1OC(=O)N(O)N1C(=O)CCC1=O MEYZIGGCNFHINA-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
PSGQCCSGKGJLRL-UHFFFAOYSA-N 4-methyl-2h-chromen-2-one Chemical compound C1=CC=CC2=C1OC(=O)C=C2C PSGQCCSGKGJLRL-UHFFFAOYSA-N 0.000 description 1
102000007469 Actins Human genes 0.000 description 1
108010085238 Actins Proteins 0.000 description 1
102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 1
108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
208000037259 Amyloid Plaque Diseases 0.000 description 1
108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
206010003694 Atrophy Diseases 0.000 description 1
241001203868 Autographa californica Species 0.000 description 1
241000271566 Aves Species 0.000 description 1
241000713842 Avian sarcoma virus Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
208000024806 Brain atrophy Diseases 0.000 description 1
101100074187 Caenorhabditis elegans lag-1 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
101710132601 Capsid protein Proteins 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
241000700198 Cavia Species 0.000 description 1
108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
239000005496 Chlorsulfuron Substances 0.000 description 1
101000584736 Ciona intestinalis Suppressor of hairless homolog Proteins 0.000 description 1
101800004419 Cleaved form Proteins 0.000 description 1
101710094648 Coat protein Proteins 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
101150074155 DHFR gene Proteins 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
102000052510 DNA-Binding Proteins Human genes 0.000 description 1
108700020911 DNA-Binding Proteins Proteins 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
102100024746 Dihydrofolate reductase Human genes 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
239000004097 EU approved flavor enhancer Substances 0.000 description 1
UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
241000991587 Enterovirus C Species 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241001524679 Escherichia virus M13 Species 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108700039691 Genetic Promoter Regions Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
102000053187 Glucuronidase Human genes 0.000 description 1
108010060309 Glucuronidase Proteins 0.000 description 1
102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
101000584743 Homo sapiens Recombining binding protein suppressor of hairless Proteins 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
241000701109 Human adenovirus 2 Species 0.000 description 1
241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010061598 Immunodeficiency Diseases 0.000 description 1
208000029462 Immunodeficiency disease Diseases 0.000 description 1
108700001097 Insect Genes Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
241000235058 Komagataella pastoris Species 0.000 description 1
ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
101710125418 Major capsid protein Proteins 0.000 description 1
101710189714 Major cell-binding factor Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
IMTUWVJPCQPJEE-IUCAKERBSA-N Met-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN IMTUWVJPCQPJEE-IUCAKERBSA-N 0.000 description 1
101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
108700005443 Microbial Genes Proteins 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
101000978776 Mus musculus Neurogenic locus notch homolog protein 1 Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
230000017418 Notch receptor processing Effects 0.000 description 1
101710141454 Nucleoprotein Proteins 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
241001494479 Pecora Species 0.000 description 1
241000286209 Phasianidae Species 0.000 description 1
101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
241000709664 Picornaviridae Species 0.000 description 1
108010047386 Pituitary Hormones Proteins 0.000 description 1
102000006877 Pituitary Hormones Human genes 0.000 description 1
241001505332 Polyomavirus sp. Species 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102000015499 Presenilins Human genes 0.000 description 1
108010050254 Presenilins Proteins 0.000 description 1
101710083689 Probable capsid protein Proteins 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
102000009572 RNA Polymerase II Human genes 0.000 description 1
108010009460 RNA Polymerase II Proteins 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
102000009661 Repressor Proteins Human genes 0.000 description 1
108010034634 Repressor Proteins Proteins 0.000 description 1
241000714474 Rous sarcoma virus Species 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
101800001111 Soluble APP-alpha Proteins 0.000 description 1
102400000571 Soluble APP-alpha Human genes 0.000 description 1
241000282887 Suidae Species 0.000 description 1
101710195626 Transcriptional activator protein Proteins 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
108700005077 Viral Genes Proteins 0.000 description 1
108010084455 Zeocin Proteins 0.000 description 1
239000003082 abrasive agent Substances 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
-1 acetic Chemical class 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
108020002494 acetyltransferase Proteins 0.000 description 1
102000005421 acetyltransferase Human genes 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000001919 adrenal effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
230000003281 allosteric effect Effects 0.000 description 1
UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000003277 amino acid sequence analysis Methods 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229940126575 aminoglycoside Drugs 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
230000003321 amplification Effects 0.000 description 1
230000003942 amyloidogenic effect Effects 0.000 description 1
238000004873 anchoring Methods 0.000 description 1
208000007502 anemia Diseases 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
229930002877 anthocyanin Natural products 0.000 description 1
235000010208 anthocyanin Nutrition 0.000 description 1
239000004410 anthocyanin Substances 0.000 description 1
150000004636 anthocyanins Chemical class 0.000 description 1
PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
150000004056 anthraquinones Chemical class 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000002421 anti-septic effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000037444 atrophy Effects 0.000 description 1
125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
239000013602 bacteriophage vector Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
108091007737 beta-secretases Proteins 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
108010006025 bovine growth hormone Proteins 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
238000007816 calorimetric assay Methods 0.000 description 1
235000013877 carbamide Nutrition 0.000 description 1
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
229960003669 carbenicillin Drugs 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
230000021523 carboxylation Effects 0.000 description 1
238000006473 carboxylation reaction Methods 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005277 cation exchange chromatography Methods 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
238000012832 cell culture technique Methods 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
210000003850 cellular structure Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000001175 cerebrospinal fluid Anatomy 0.000 description 1
239000013522 chelant Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
VJYIFXVZLXQVHO-UHFFFAOYSA-N chlorsulfuron Chemical compound COC1=NC(C)=NC(NC(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)=N1 VJYIFXVZLXQVHO-UHFFFAOYSA-N 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
239000012501 chromatography medium Substances 0.000 description 1
239000003593 chromogenic compound Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000012790 confirmation Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
230000001066 destructive effect Effects 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
108020001096 dihydrofolate reductase Proteins 0.000 description 1
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001035 drying Methods 0.000 description 1
UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
210000002472 endoplasmic reticulum Anatomy 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
238000002270 exclusion chromatography Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000004088 foaming agent Substances 0.000 description 1
235000019264 food flavour enhancer Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
239000008103 glucose Substances 0.000 description 1
102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
238000003505 heat denaturation Methods 0.000 description 1
230000011132 hemopoiesis Effects 0.000 description 1
101150113423 hisD gene Proteins 0.000 description 1
102000046783 human APP Human genes 0.000 description 1
239000003906 humectant Substances 0.000 description 1
238000009396 hybridization Methods 0.000 description 1
229910052588 hydroxylapatite Inorganic materials 0.000 description 1
238000012872 hydroxylapatite chromatography Methods 0.000 description 1
239000000960 hypophysis hormone Substances 0.000 description 1
239000000815 hypotonic solution Substances 0.000 description 1
230000014726 immortalization of host cell Effects 0.000 description 1
230000007813 immunodeficiency Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000002513 implantation Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000002601 intratumoral effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
235000014413 iron hydroxide Nutrition 0.000 description 1
NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical class [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
238000005304 joining Methods 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000003041 laboratory chemical Substances 0.000 description 1
150000002605 large molecules Chemical class 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
210000002751 lymph Anatomy 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
230000005012 migration Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000003068 molecular probe Substances 0.000 description 1
239000003471 mutagenic agent Substances 0.000 description 1
229960000951 mycophenolic acid Drugs 0.000 description 1
HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
210000004898 n-terminal fragment Anatomy 0.000 description 1
210000004897 n-terminal region Anatomy 0.000 description 1
239000013642 negative control Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000002547 new drug Substances 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
108010079892 phosphoglycerol kinase Proteins 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920002704 polyhistidine Polymers 0.000 description 1
229930001118 polyketide hybrid Natural products 0.000 description 1
125000003308 polyketide hybrid group Chemical group 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
230000004481 post-translational protein modification Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000007686 potassium Nutrition 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
DOKHEARVIDLSFF-UHFFFAOYSA-N prop-1-en-1-ol Chemical group CC=CO DOKHEARVIDLSFF-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
230000004952 protein activity Effects 0.000 description 1
108020001580 protein domains Proteins 0.000 description 1
230000007065 protein hydrolysis Effects 0.000 description 1
238000000164 protein isolation Methods 0.000 description 1
230000012743 protein tagging Effects 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
229950010131 puromycin Drugs 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
239000006152 selective media Substances 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
230000003584 silencer Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000002689 soil Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
230000010473 stable expression Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
230000008685 targeting Effects 0.000 description 1
238000010257 thawing Methods 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
229960003766 thrombin (human) Drugs 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000005026 transcription initiation Effects 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
101150081616 trpB gene Proteins 0.000 description 1
101150111232 trpB-1 gene Proteins 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
241001515965 unidentified phage Species 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003501 vero cell Anatomy 0.000 description 1
239000013603 viral vector Substances 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
238000012800 visualization Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/71—Fusion polypeptide containing domain for protein-protein interaction containing domain for transcriptional activaation, e.g. VP16
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
General Health & Medical Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Zoology (AREA)
Medicinal Chemistry (AREA)
Wood Science & Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Gastroenterology & Hepatology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Microbiology (AREA)
Toxicology (AREA)
Physics & Mathematics (AREA)
Immunology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Analytical Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Psychiatry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Hospice & Palliative Care (AREA)
Plant Pathology (AREA)
Enzymes And Modification Thereof (AREA)
Peptides Or Proteins (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Investigating Or Analysing Biological Materials (AREA)

HR20050461A 2002-11-26 2005-05-24 Soluble notch-based substrates for gamma secretase and methods and compositions for using same HRP20050461A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US42920602P	2002-11-26	2002-11-26
PCT/IB2003/005233 WO2004048578A1 (en)	2002-11-26	2003-11-17	Soluble notch-based substrates for gamma secretase and methods and compositions for using same

Publications (1)

Publication Number	Publication Date
HRP20050461A2 true HRP20050461A2 (en)	2005-08-31

Family

ID=32393521

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20050461A HRP20050461A2 (en)	2002-11-26	2005-05-24	Soluble notch-based substrates for gamma secretase and methods and compositions for using same

Country Status (14)

Country	Link
US (1)	US20110098227A1 (zh)
EP (1)	EP1567647B1 (zh)
JP (1)	JP2006508653A (zh)
KR (1)	KR20050085177A (zh)
CN (1)	CN1717485A (zh)
AT (1)	ATE374824T1 (zh)
AU (1)	AU2003283619A1 (zh)
CA (1)	CA2505764A1 (zh)
DE (1)	DE60316718T2 (zh)
ES (1)	ES2293047T3 (zh)
HR (1)	HRP20050461A2 (zh)
NO (1)	NO20052552L (zh)
RU (1)	RU2005115973A (zh)
WO (1)	WO2004048578A1 (zh)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0518232D0 (en) *	2005-09-07	2005-10-19	Merck Sharp & Dohme	New methods
WO2008150010A1 (ja) *	2007-06-08	2008-12-11	Eisai R & D Management Co., Ltd.	γ-セクレターゼの新規基質EphA4を利用したスクリーニング方法
EP2219028B1 (en)	2007-11-15	2012-09-12	Eisai R&D Management Co., Ltd.	Screening method utilizing novel substrate epha7 for gamma-secretase
US9023767B2 (en) *	2009-05-07	2015-05-05	Memorial Sloan-Kettering Cancer Center	γ-Secretase substrates and methods of use
US9632088B2 (en) *	2010-09-07	2017-04-25	Memorial Sloan-Kettering Cancer Center	Methods and compositions for gamma-secretase assay
EP2653552B1 (en)	2010-12-17	2016-10-19	Eisai R&D Management Co., Ltd.	SCREENING METHOD USING GELATINASE-MEDIATED EphA4 CLEAVAGE REACTION AS AN INDICATOR
JP5961608B2 (ja)	2011-04-25	2016-08-02	エーザイ・アール・アンド・ディー・マネジメント株式会社	ＥｐｈＡ４細胞外ドメインの測定による認知機能障害を伴う神経系疾患の検出方法
TWI866304B (zh)	2019-07-01	2024-12-11	日商衛材R&D企管股份有限公司	抗EphA4抗體

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1257633A1 (en) *	2000-02-25	2002-11-20	Vlaams Interuniversitair Instituut voor Biotechnologie vzw.	Presenilin deficient multipotent cell lines and screening methods for intramembrane regulated proteolytic activities using these lines

2003
- 2003-11-17 CN CNA2003801042336A patent/CN1717485A/zh active Pending
- 2003-11-17 EP EP03775599A patent/EP1567647B1/en not_active Expired - Lifetime
- 2003-11-17 CA CA002505764A patent/CA2505764A1/en not_active Abandoned
- 2003-11-17 AU AU2003283619A patent/AU2003283619A1/en not_active Abandoned
- 2003-11-17 DE DE60316718T patent/DE60316718T2/de not_active Expired - Fee Related
- 2003-11-17 RU RU2005115973/13A patent/RU2005115973A/ru not_active Application Discontinuation
- 2003-11-17 AT AT03775599T patent/ATE374824T1/de not_active IP Right Cessation
- 2003-11-17 ES ES03775599T patent/ES2293047T3/es not_active Expired - Lifetime
- 2003-11-17 KR KR1020057009579A patent/KR20050085177A/ko active IP Right Grant
- 2003-11-17 WO PCT/IB2003/005233 patent/WO2004048578A1/en active IP Right Grant
- 2003-11-17 JP JP2004554808A patent/JP2006508653A/ja active Pending
- 2003-11-19 US US10/717,244 patent/US20110098227A1/en not_active Abandoned
2005
- 2005-05-24 HR HR20050461A patent/HRP20050461A2/hr not_active Application Discontinuation
- 2005-05-26 NO NO20052552A patent/NO20052552L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
ES2293047T3 (es)	2008-03-16
ATE374824T1 (de)	2007-10-15
US20110098227A1 (en)	2011-04-28
EP1567647B1 (en)	2007-10-03
CA2505764A1 (en)	2004-06-10
WO2004048578A1 (en)	2004-06-10
EP1567647A1 (en)	2005-08-31
DE60316718T2 (de)	2008-01-24
AU2003283619A1 (en)	2004-06-18
NO20052552D0 (no)	2005-05-26
RU2005115973A (ru)	2005-12-20
CN1717485A (zh)	2006-01-04
JP2006508653A (ja)	2006-03-16
KR20050085177A (ko)	2005-08-29
NO20052552L (no)	2005-08-25
DE60316718D1 (de)	2007-11-15

Publication	Publication Date	Title
EP1115874B1 (en)	2009-01-07	Alzheimer's disease secretase
US7368536B2 (en)	2008-05-06	Alzheimer's disease secretase, APP substrates therefor, and uses therefor
US20080299596A1 (en)	2008-12-04	Substrates and assays for beta-secretase activity
EP1224297A2 (en)	2002-07-24	Alzheimer's disease secretase, app substrates therefor, and uses therefor
US20110294149A1 (en)	2011-12-01	Alzheimer's Disease Secretase, APP Substrates Therefor, and Uses Therefor
HRP20050461A2 (en)	2005-08-31	Soluble notch-based substrates for gamma secretase and methods and compositions for using same
AU2005225037B2 (en)	2008-05-22	Alzheimer's disease secretase, APP substrates therefor, and uses therefor
AU2007203091A1 (en)	2007-07-19	Substrates and assays for beta-secretase activity
EP1939297A1 (en)	2008-07-02	Alzheimer's disease secretase

Legal Events

Date	Code	Title	Description
2005-07-22	ARAI	Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
2005-08-31	A1OB	Publication of a patent application
2007-10-18	ODRP	Renewal fee for the maintenance of a patent	Payment date: 20071018 Year of fee payment: 5
2009-05-25	OBST	Application withdrawn