Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDC00067

Target Information
NameCathepsin S    
Type of targetDiscontinued target    
SynonymsCysteine protease cathepsin S    
DiseaseAutoimmune diseases
[ICD9: 279.4   ICD10: D84.9, M35.9]
[1][2]
Psoriasis and Psoriatic Disorders
[ICD9: 696   ICD10: L40]
[3]
Drug(s)SAR114137Phase IOsteoarthritic pain
CRA-028129Discontinued in Phase IPsoriasis and Psoriatic Disorders[4]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC 3.4.22.27
PathwayAntigen processing and presentation
Lysosome
UniProt IDP25774
PDB Structure1BXF; 1GLO; 1MS6; 1NPZ; 1NQC; 2C0Y; 2F1G; 2FQ9; 2FRA; 2FRQ; 2FT2; 2FUD; 2FYE; 2G6D; 2G7Y; 2H7J; 2HH5; 2HHN; 2HXZ; 2OP3; 2R9M; 2R9N; 2R9O; 3IEJ; 3KWN; 3MPE; 3MPF; 3N3G; 3N4C; 3OVX.    
FunctionThiol protease. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin l and cathepsin n.    
SequenceMKRLVCVLLVCSSAVAQLHKDPTLDHHWHLWKKTYGKQYKEKNEEAVRRLIWEKNLKFVM LHNLEHSMGMHSYDLGMNHLGDMTSEEVMSLMSSLRVPSQWQRNITYKSNPNRILPDSVD WREKGCVTEVKYQGSCGACWAFSAVGALEAQLKLKTGKLVSLSAQNLVDCSTEKYGNKGC NGGFMTTAFQYIIDNKGIDSDASYPYKAMDQKCQYDSKYRAATCSKYTELPYGREDVLKE AVANKGPVSVGVDARHPSFFLYRSGVYYEPSCTQNVNHGVLVVGYGDLNGKEYWLVKNSW GHNFGEEGYIRMARNKGNHCGIASFPSYPEI
Related US Patent6,313,119
6,420,364
6,455,502
6,476,026
6,492,362
6,506,733
6,525,036
6,525,052
6,576,630
6,593,327
6,608,057
6,635,621
6,649,642
6,730,671
Target ValidationClick to Find Target Validation Information.    
Inhibitor2-[ (2',3',4'-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL[5]
4-cycloheptyl-6-propylpyrimidine-2-carbonitrile[6]
4-cyclooctyl-6-propylpyrimidine-2-carbonitrile[6]
4-propyl-6-m-tolylpyrimidine-2-carbonitrile[7]
6- (3-[8]
Ac-hPhe-Leu-Ala-LeuVSMe[9]
Ac-hPhe-Leu-Gly-LeuVSMe[9]
Ac-hPhe-Leu-Phe-LeuVSMe[9]
BOCEPREVIR[10]
CRA-028129[4]
Cbz-Glu (OtBu)-Ala-LeuVSMe[9]
Cbz-Ile-Leu-Ala-LeuVSMe[9]
Cbz-Ile-MetO2-Ala-LeuVSMe[9]
Cbz-Ile-Phe-Ala-LeuVSMe[9]
Cbz-Ile-Pro-Ala-LeuVSMe[9]
Cbz-Ile-hPhe-Ala-LeuVSMe[9]
Cbz-Ile-t-ButylGln-Ala-LeuVSMe[9]
Cbz-Ile-t-ButylhomoGlu-Ala-LeuVSMe[9]
Clik60[2]
E-64[11]
Fucose[12]
GNF-PF-5434[13]
L-006235-1[14]
L-873724[15]
N- (1-oxobutan-2-yl)-3-[16]
N- (2-naphthylsulfonyl)-glycyl-glycine-nitrile[17]
N- (4-phenylbenzoyl)-phenylalanyl-glycine-nitrile[17]
N- (benzyloxycarbonyl)-leucyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-isoleucyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-leucyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-methionyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-norleucyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-norvalyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-tyrosyl-glycine-nitrile[17]
N- (tert-butoxycarbonyl)-valyl-glycine-nitrile[17]
N-acetyl-phenylalanyl-glycine-nitrile[17]
N-benzoyl-phenylalanyl-glycine-nitrile[17]
P2,P3 Ketoamide derivative[18]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Specificity determinants of human cathepsin s revealed by crystal structures of complexes. Biochemistry. 2003 Mar 25;42(11):3203-13. To Reference
Ref 2Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. J Clin Invest. 2002 Aug;110(3):361-9. To Reference
Ref 3CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. To Reference
Ref 4Phase I clinical trial for cathepsin S inhibitor for psoriasis begins. Celera Genomics. 2005 To Reference
Ref 5Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 6Bioorg 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. To Reference
Ref 7Bioorg 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. To Reference
Ref 8Bioorg 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. To Reference
Ref 9J 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. To Reference
Ref 10Antimicrob Agents Chemother. 2010 Jan;54(1):305-11. Epub 2009 Oct 19.MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease. To Reference
Ref 11Baculoviral expression and characterization of rodent cathepsin S. Protein Expr Purif. 2001 Oct;23(1):45-54. To Reference
Ref 12Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 13Bioorg Med Chem. 2009 Feb 1;17(3):1064-70. Epub 2008 Feb 7.Substrate optimization for monitoring cathepsin C activity in live cells. To Reference
Ref 14J 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. To Reference
Ref 15Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. Epub 2007 Jun 10.The identification of potent, selective, and bioavailable cathepsin S inhibitors. To Reference
Ref 16Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. Epub 2010 Oct 26.Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors. To Reference
Ref 17J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. To Reference
Ref 18Bioorg 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. To Reference



 

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