Target Information
Target General Infomation | |||||
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Target ID |
T68290
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Former ID |
TTDC00067
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Target Name |
Cathepsin S
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Gene Name |
CTSS
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Synonyms |
Cysteine protease cathepsin S; CTSS
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Target Type |
Clinical Trial
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Disease | Autoimmune diabetes [ICD10: E08-E13] | ||||
Asthma [ICD10: J45] | |||||
Cardiovascular disorder [ICD10: I00-I99] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | |||||
Psoriatic disorder [ICD9: 696; ICD10: L40] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Function |
Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond- specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.
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BioChemical Class |
Peptidase
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Target Validation |
T68290
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UniProt ID | |||||
EC Number |
EC 3.4.22.27
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Sequence |
MKRLVCVLLVCSSAVAQLHKDPTLDHHWHLWKKTYGKQYKEKNEEAVRRLIWEKNLKFVM
LHNLEHSMGMHSYDLGMNHLGDMTSEEVMSLMSSLRVPSQWQRNITYKSNPNRILPDSVD WREKGCVTEVKYQGSCGACWAFSAVGALEAQLKLKTGKLVSLSAQNLVDCSTEKYGNKGC NGGFMTTAFQYIIDNKGIDSDASYPYKAMDQKCQYDSKYRAATCSKYTELPYGREDVLKE AVANKGPVSVGVDARHPSFFLYRSGVYYEPSCTQNVNHGVLVVGYGDLNGKEYWLVKNSW GHNFGEEGYIRMARNKGNHCGIASFPSYPEI |
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Drugs and Mode of Action | |||||
Drug(s) | SAR-114137 | Drug Info | Phase 1 | Pain | [532135] |
VBY- 036 | Drug Info | Phase 1 | Neuropathic pain | [524350] | |
VBY- 891 | Drug Info | Phase 1 | Autoimmune diabetes | [524438] | |
VBY-129 | Drug Info | Phase 1 | Autoimmune diabetes | [551766] | |
RG-7236 | Drug Info | Discontinued in Phase 1 | Cardiovascular disorder | [549201] | |
CRA-028129 | Drug Info | Terminated | Psoriatic disorder | [548110] | |
Inhibitor | 2-[(2',3',4'-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL | Drug Info | [551374] | ||
4-cycloheptyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [530717] | |||
4-cyclooctyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [530717] | |||
4-propyl-6-m-tolylpyrimidine-2-carbonitrile | Drug Info | [531005] | |||
6-(3-(trifluoromethyl)phenyl)picolinonitrile | Drug Info | [530989] | |||
Ac-hPhe-Leu-Ala-LeuVSMe | Drug Info | [528196] | |||
Ac-hPhe-Leu-Gly-LeuVSMe | Drug Info | [528196] | |||
Ac-hPhe-Leu-Phe-LeuVSMe | Drug Info | [528196] | |||
AM-3840 | Drug Info | [543601] | |||
BF/PC-18 | Drug Info | [543601] | |||
Cbz-Glu(OtBu)-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-hPhe-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-Leu-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-MetO2-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-Phe-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-Pro-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-t-ButylGln-Ala-LeuVSMe | Drug Info | [528196] | |||
Cbz-Ile-t-ButylhomoGlu-Ala-LeuVSMe | Drug Info | [528196] | |||
Clik60 | Drug Info | [535523] | |||
compound (R)-26 | Drug Info | [531940] | |||
CRA-028129 | Drug Info | [551432] | |||
E-64 | Drug Info | [535267] | |||
Fucose | Drug Info | [551393] | |||
GNF-PF-5434 | Drug Info | [529350] | |||
JNJ-10329670 | Drug Info | [543601] | |||
L-006235-1 | Drug Info | [527882] | |||
L-873724 | Drug Info | [528921] | |||
N-(1-oxobutan-2-yl)-3-(trifluoromethyl)benzamide | Drug Info | [531241] | |||
N-(2-naphthylsulfonyl)-glycyl-glycine-nitrile | Drug Info | [527885] | |||
N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
N-(benzyloxycarbonyl)-leucyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-norvalyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-tyrosyl-glycine-nitrile | Drug Info | [527885] | |||
N-(tert-butoxycarbonyl)-valyl-glycine-nitrile | Drug Info | [527885] | |||
N-acetyl-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
N-benzoyl-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
P2,P3 Ketoamide derivative | Drug Info | [527197] | |||
RG-7236 | Drug Info | [543601] | |||
SAR-114137 | Drug Info | [532135] | |||
VBY- 036 | Drug Info | [550109] | |||
VBY- 285 | Drug Info | [543601] | |||
VBY-129 | Drug Info | [551767] | |||
Modulator | VBY- 891 | Drug Info | [543601] | ||
Pathways | |||||
KEGG Pathway | Lysosome | ||||
Phagosome | |||||
Antigen processing and presentation | |||||
Tuberculosis | |||||
NetPath Pathway | Leptin Signaling Pathway | ||||
IL2 Signaling Pathway | |||||
Reactome | Endosomal/Vacuolar pathway | ||||
Degradation of the extracellular matrix | |||||
Trafficking and processing of endosomal TLR | |||||
Assembly of collagen fibrils and other multimeric structures | |||||
MHC class II antigen presentation | |||||
WikiPathways | Class I MHC mediated antigen processing & | ||||
presentation | |||||
Trafficking and processing of endosomal TLR | |||||
References | |||||
Ref 524350 | ClinicalTrials.gov (NCT01892891) Safety Study of VBY-036 in Healthy Volunteers After 7 Days of Oral Dosing. U.S. National Institutes of Health. | ||||
Ref 524438 | ClinicalTrials.gov (NCT01947738) Safety Study of VBY-891 in Healthy Volunteers After Single or Multiple (7 Days) of Oral Dosing (VBY891P1). U.S. National Institutes of Health. | ||||
Ref 532135 | From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor. Eur J Pharm Biopharm. 2013 Apr;83(3):436-48. | ||||
Ref 548110 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022029) | ||||
Ref 527197 | Bioorg Med Chem Lett. 2004 Oct 4;14(19):4897-902.Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions. | ||||
Ref 527882 | J Med Chem. 2005 Dec 1;48(24):7535-43.Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. | ||||
Ref 527885 | J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. | ||||
Ref 528196 | J Med Chem. 2006 May 18;49(10):2953-68.Optimization of subsite binding to the beta5 subunit of the human 20S proteasome using vinyl sulfones and 2-keto-1,3,4-oxadiazoles: syntheses and cellular properties of potent, selective proteasome inhibitors. | ||||
Ref 528921 | Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. Epub 2007 Jun 10.The identification of potent, selective, and bioavailable cathepsin S inhibitors. | ||||
Ref 529350 | Bioorg Med Chem. 2009 Feb 1;17(3):1064-70. Epub 2008 Feb 7.Substrate optimization for monitoring cathepsin C activity in live cells. | ||||
Ref 530717 | Bioorg Med Chem Lett. 2010 Mar 1;20(5):1524-7. Epub 2010 Jan 25.Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors. | ||||
Ref 530989 | Bioorg Med Chem Lett. 2010 Aug 1;20(15):4507-10. Epub 2010 Jun 10.4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important. | ||||
Ref 531005 | Bioorg Med Chem Lett. 2010 Aug 1;20(15):4447-50. Epub 2010 Jun 15.2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors. | ||||
Ref 531241 | Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. Epub 2010 Oct 26.Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors. | ||||
Ref 531940 | Selective nitrile inhibitors to modulate the proteolytic synergism of cathepsins S and F. J Med Chem. 2012 Jun 28;55(12):5982-6. | ||||
Ref 532135 | From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor. Eur J Pharm Biopharm. 2013 Apr;83(3):436-48. | ||||
Ref 535267 | Baculoviral expression and characterization of rodent cathepsin S. Protein Expr Purif. 2001 Oct;23(1):45-54. | ||||
Ref 535523 | Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. J Clin Invest. 2002 Aug;110(3):361-9. | ||||
Ref 543601 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2353). |
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