Target Information
Target General Infomation | |||||
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Target ID |
T11388
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Former ID |
TTDC00068
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Target Name |
Cathepsin K
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Gene Name |
CTSK
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Synonyms |
Cathepsin O; Cathepsin O2; Cathepsin X; CTSK
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Target Type |
Clinical Trial
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Disease | Asthma [ICD10: J45] | ||||
Bone metastases [ICD9: 198.5; ICD10: C79.51] | |||||
Bone disease [ICD10: M00-M99] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Osteoporosis [ICD9: 733.0, V07.4; ICD10: M80-M81, Z79.890] | |||||
Osteopenia [ICD9: 733.9; ICD10: M85.8] | |||||
Ostereoporosis [ICD9: 733; ICD10: M80-M81] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Function |
Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
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BioChemical Class |
Peptidase
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Target Validation |
T11388
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UniProt ID | |||||
EC Number |
EC 3.4.22.38
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Sequence |
MWGLKVLLLPVVSFALYPEEILDTHWELWKKTHRKQYNNKVDEISRRLIWEKNLKYISIH
NLEASLGVHTYELAMNHLGDMTSEEVVQKMTGLKVPLSHSRSNDTLYIPEWEGRAPDSVD YRKKGYVTPVKNQGQCGSCWAFSSVGALEGQLKKKTGKLLNLSPQNLVDCVSENDGCGGG YMTNAFQYVQKNRGIDSEDAYPYVGQEESCMYNPTGKAAKCRGYREIPEGNEKALKRAVA RVGPVSVAIDASLTSFQFYSKGVYYDESCNSDNLNHAVLAVGYGIQKGNKHWIIKNSWGE NWGNKGYILMARNKNNACGIANLASFPKM |
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Drugs and Mode of Action | |||||
Drug(s) | Odanacatib | Drug Info | Phase 1 | Ostereoporosis | [548318] |
SAR-114137 | Drug Info | Phase 1 | Pain | [532135] | |
VEL-0230 | Drug Info | Phase 1 | Rheumatoid arthritis | [551545] | |
Balicatib | Drug Info | Discontinued in Phase 2 | Osteoporosis | [536957], [542791] | |
ONO-5334 | Drug Info | Discontinued in Phase 2 | Osteopenia | [522118] | |
Relacatib | Drug Info | Discontinued in Phase 2 | Bone metastases | [536957], [542792] | |
MIV-701 | Drug Info | Discontinued in Phase 1 | Osteoporosis | [547449] | |
Relacatib | Drug Info | Discontinued in Phase 1 | Osteoporosis | [536957], [542792] | |
Inhibitor | (S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate | Drug Info | [527872] | ||
(S)-tert-butyl 1-oxohexan-2-ylcarbamate | Drug Info | [527872] | |||
(S)-tert-butyl 4-methyl-1-oxopentan-2-ylcarbamate | Drug Info | [527872] | |||
2-cyclohexylamino-pyridine-2-carbonitrile | Drug Info | [528643] | |||
2-cyclohexylamino-pyrimidine-4-carbonitrile | Drug Info | [528643] | |||
3-Amino-5-Phenylpentane | Drug Info | [551393] | |||
4-cycloheptyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [530717] | |||
4-cyclohexyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [530717] | |||
4-cyclohexylamino-pyrimidine-2-carbonitrile | Drug Info | [528643] | |||
4-cyclooctyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [530717] | |||
4-phenyl-6-propylpyrimidine-2-carbonitrile | Drug Info | [531005] | |||
4-propyl-6-m-tolylpyrimidine-2-carbonitrile | Drug Info | [531005] | |||
AM-3701 | Drug Info | [543600] | |||
Balicatib | Drug Info | [536957] | |||
BF/PC-21 | Drug Info | [543600] | |||
Boc-Agly-Val-Agly-OEt | Drug Info | [526417] | |||
compound 1b | Drug Info | [527872] | |||
GNF-PF-5434 | Drug Info | [529350] | |||
GW-2592X | Drug Info | [543600] | |||
L-006235-1 | Drug Info | [527882] | |||
L-873724 | Drug Info | [536609] | |||
MIV-701 | Drug Info | [551164] | |||
N-(1-((cyanomethyl)carbamoyl)cyclohexyl)benzamide | Drug Info | [528002] | |||
N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
N-(benzyloxycarbonyl)-leucyl-glycine-nitrile | Drug Info | [527885] | |||
N-(cyanomethyl)cyclohex-1-ene-1-carboxamide | Drug Info | [528002] | |||
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)-valyl-glycine-nitrile | Drug Info | [527885] | |||
N-acetyl-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
N-benzoyl-phenylalanyl-glycine-nitrile | Drug Info | [527885] | |||
Odanacatib | Drug Info | [536569], [549718] | |||
ONO-5334 | Drug Info | [531317], [532506] | |||
P2,P3 Ketoamide derivative | Drug Info | [527197] | |||
Peptide aldehydes | Drug Info | [538046] | |||
Pyrrolidine-1-carbonitrile | Drug Info | [527556] | |||
Relacatib | Drug Info | [536193], [536274], [536609] | |||
SAR-114137 | Drug Info | [532135] | |||
Tert-butyl (2S)-1-cyanopyrrolidine-2-carboxylate | Drug Info | [527556] | |||
TERT-BUTYL 2-CYANO-2-METHYLHYDRAZINECARBOXYLATE | Drug Info | [551374] | |||
Tert-Butyl(1s)-1-Cyclohexyl-2-Oxoethylcarbamate | Drug Info | [551374] | |||
VEL-0230 | Drug Info | [526178] | |||
Z-Ala-Leu-His-Agly-Ile-Val-OMe | Drug Info | [526417] | |||
Z-Ala-Leu-lle-Agly-Ile-Val-NHBzl | Drug Info | [526417] | |||
Z-Ala-Leu-lle-Agly-Ile-Val-OMe | Drug Info | [526417] | |||
Z-Ala-Leu-Nal-Agly-Ile-Val-OMe | Drug Info | [526417] | |||
Z-Ala-Leu-Phe-Agly-Ile-Val-OMe | Drug Info | [526417] | |||
Z-Ala-Leu-Tyr(Me)-Agly-Ile-Val-OMe | Drug Info | [526417] | |||
Z-Arg-Leu-Val-Agly-Ala-Gly-NH2 | Drug Info | [526417] | |||
Z-Arg-Leu-Val-Agly-Ile-Val-Trp-NH2 | Drug Info | [526417] | |||
Z-Arg-Leu-Val-Agly-Ileu-Val-OMe | Drug Info | [526417] | |||
Z-Arg-Leu-Val-Agly-Trp-Val-Ala-NH2 | Drug Info | [526417] | |||
Z-Arg-Leu-Val-Agly-Val-Ala-NH2 | Drug Info | [526417] | |||
Z-leu-Val-Agly-Val-OBzl | Drug Info | [526417] | |||
Modulator | MIV-710 | Drug Info | [543600] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Lysosome | ||||
Osteoclast differentiation | |||||
Toll-like receptor signaling pathway | |||||
Rheumatoid arthritis | |||||
NetPath Pathway | TGF_beta_Receptor Signaling Pathway | ||||
RANKL Signaling Pathway | |||||
IL2 Signaling Pathway | |||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
Trafficking and processing of endosomal TLR | |||||
MHC class II antigen presentation | |||||
WikiPathways | RANKL/RANK Signaling Pathway | ||||
Osteoclast Signaling | |||||
References | |||||
Ref 522118 | ClinicalTrials.gov (NCT00532337) Controlled Study of ONO-5334 in Postmenopausal Women With Osteopenia or Osteoporosis. 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 536957 | Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27. | ||||
Ref 542791 | (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. (Ligand id: 7861). | ||||
Ref 542792 | (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. (Ligand id: 7862). | ||||
Ref 547449 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016480) | ||||
Ref 526178 | Discovery and parallel synthesis of a new class of cathepsin K inhibitors. Bioorg Med Chem Lett. 2001 Nov 19;11(22):2951-4. | ||||
Ref 526417 | J Med Chem. 2002 Sep 12;45(19):4202-11.Azapeptides structurally based upon inhibitory sites of cystatins as potent and selective inhibitors of cysteine proteases. | ||||
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 527556 | Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43.Acyclic cyanamide-based inhibitors of cathepsin K. | ||||
Ref 527872 | Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. Epub 2005 Nov 15.Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?. | ||||
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 528002 | J Med Chem. 2006 Feb 9;49(3):1066-79.Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K. | ||||
Ref 528643 | J Med Chem. 2007 Feb 22;50(4):591-4. Epub 2007 Jan 27.2-Cyano-pyrimidines: a new chemotype for inhibitors of the cysteine protease cathepsin K. | ||||
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 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 531317 | New approach for osteoporosis treatment: cathepsin K inhibitor, ONO-5334. Clin Calcium. 2011 Jan;21(1):64-9. | ||||
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 532506 | Population pharmacokinetic and pharmacodynamic modeling of different formulations of ONO-5334, cathepsin K inhibitor, in Caucasian and Japanese postmenopausal females. J Clin Pharmacol. 2014 Jan;54(1):23-34. | ||||
Ref 536193 | Structure activity relationships of 5-, 6-, and 7-methyl-substituted azepan-3-one cathepsin K inhibitors. J Med Chem. 2006 Mar 9;49(5):1597-612. | ||||
Ref 536274 | A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys. Bone. 2007 Jan;40(1):122-31. Epub 2006 Sep 7. | ||||
Ref 536569 | Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther. 2008 Jan;83(1):172-6. Epub 2007 Dec 12. | ||||
Ref 536609 | The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8. Epub 2008 Jan 15. | ||||
Ref 536957 | Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27. | ||||
Ref 538046 | Peptide aldehyde inhibitors of cathepsin K inhibit bone resorption both in vitro and in vivo. J Bone Miner Res. 1997 Sep;12(9):1396-406. | ||||
Ref 543600 | (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: 2350). | ||||
Ref 549718 | A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8. |
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