Target Validation Information
Target ID T11388
Target Name Cathepsin K
Target Type
Clinical Trial
Drug Potency against Target 2-cyclohexylamino-pyrimidine-4-carbonitrile Drug Info IC50 = 120 nM [528643]
P2,P3 Ketoamide derivative Drug Info IC50 = 40 nM [527197]
4-cycloheptyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 84 nM [530717]
Z-Arg-Leu-Val-Agly-Val-Ala-NH2 Drug Info Ki = 2.13 nM [526417]
Z-Arg-Leu-Val-Agly-Ileu-Val-OMe Drug Info Ki = 21 nM [526417]
Boc-Agly-Val-Agly-OEt Drug Info Ki = 61 nM [526417]
Z-Ala-Leu-lle-Agly-Ile-Val-OMe Drug Info Ki = 2.12 nM [526417]
Z-Arg-Leu-Val-Agly-Ile-Val-Trp-NH2 Drug Info Ki = 72 nM [526417]
Z-Arg-Leu-Val-Agly-Trp-Val-Ala-NH2 Drug Info Ki = 100 nM [526417]
4-propyl-6-m-tolylpyrimidine-2-carbonitrile Drug Info IC50 = 182 nM [531005]
N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile Drug Info Ki = 300 nM [527885]
N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile Drug Info Ki = 5800 nM [527885]
4-cyclohexyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 680 nM [530717]
N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile Drug Info Ki = 1270 nM [527885]
(S)-tert-butyl 1-oxohexan-2-ylcarbamate Drug Info IC50 = 51 nM [527872]
N-(benzyloxycarbonyl)-leucyl-glycine-nitrile Drug Info Ki = 35 nM [527885]
GNF-PF-5434 Drug Info Ki = 1.2 nM [529350]
4-phenyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 1122 nM [531005]
L-873724 Drug Info IC50 = 6.1 nM [529711]
Odanacatib Drug Info IC50 = 0.2 nM [536609]
Z-leu-Val-Agly-Val-OBzl Drug Info Ki = 34 nM [526417]
Z-Ala-Leu-lle-Agly-Ile-Val-NHBzl Drug Info Ki = 2.45 nM [526417]
Z-Ala-Leu-His-Agly-Ile-Val-OMe Drug Info Ki = 0.86 nM [526417]
Z-Arg-Leu-Val-Agly-Ala-Gly-NH2 Drug Info Ki = 6.76 nM [526417]
Z-Ala-Leu-Nal-Agly-Ile-Val-OMe Drug Info Ki = 5.75 nM [526417]
Z-Ala-Leu-Phe-Agly-Ile-Val-OMe Drug Info Ki = 0.18 nM [526417]
L-006235-1 Drug Info IC50 = 0.5 nM [527882]
4-cyclooctyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 11 nM [530717]
Pyrrolidine-1-carbonitrile Drug Info Ki = 2100 nM [527556]
Tert-butyl (2S)-1-cyanopyrrolidine-2-carboxylate Drug Info Ki = 60 nM [527556]
Z-Ala-Leu-Tyr(Me)-Agly-Ile-Val-OMe Drug Info Ki = 8.42 nM [526417]
N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile Drug Info Ki = 730 nM [527885]
N-(tert-butoxycarbonyl)-norvalyl-glycine-nitrile Drug Info Ki = 1100 nM [527885]
N-benzoyl-phenylalanyl-glycine-nitrile Drug Info Ki = 1500 nM [527885]
N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile Drug Info Ki = 120 nM [527885]
(S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate Drug Info IC50 = 0.35 nM [527872]
N-acetyl-phenylalanyl-glycine-nitrile Drug Info Ki = 7500 nM [527885]
BOCEPREVIR Drug Info IC50 = 40 nM [530459]
Relacatib Drug Info Ki = 0.75 nM
2-cyclohexylamino-pyridine-2-carbonitrile Drug Info IC50 = 1000 nM [528643]
4-cyclohexylamino-pyrimidine-2-carbonitrile Drug Info IC50 = 170 nM [528643]
N-(tert-butoxycarbonyl)-valyl-glycine-nitrile Drug Info Ki = 6500 nM [527885]
L-873724 Drug Info IC50 = 0.8 nM [536609]
(S)-tert-butyl 4-methyl-1-oxopentan-2-ylcarbamate Drug Info IC50 = 31 nM [527872]
N-(1-((cyanomethyl)carbamoyl)cyclohexyl)benzamide Drug Info IC50 = 78 nM [528002]
N-(cyanomethyl)cyclohex-1-ene-1-carboxamide Drug Info IC50 = 3400 nM [528002]
Action against Disease Model Odanacatib Odanacatib show greater than 100-fold h uMan Cat K enzyme (IC50= 0.2nM) selectivity and have similar IC(50) values against each cathepsin in cell-based and enzyme assays. [537348] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Cathepsin K-deficient mice, generated by targeted disruption of the cathepsin K gene exhibit an osteopetrotic phenotype characterized by thick bone trabeculae. [537348]
References
Ref 537348Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol Chem. 2009 May 20.
Ref 528643J 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 527197Bioorg 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 530717Bioorg 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 526417J 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 526417J 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 526417J 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 526417J 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 526417J 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 526417J 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 531005Bioorg 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 530717Bioorg 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527872Bioorg 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 529350Bioorg Med Chem. 2009 Feb 1;17(3):1064-70. Epub 2008 Feb 7.Substrate optimization for monitoring cathepsin C activity in live cells.
Ref 531005Bioorg 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 529711J Med Chem. 2008 Oct 23;51(20):6410-20. Epub 2008 Sep 24.Identification of a nonbasic, nitrile-containing cathepsin K inhibitor (MK-1256) that is efficacious in a monkey model of osteoporosis.
Ref 536609The 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 526417J 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 526417J 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 526417J 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 526417J 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 526417J 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 526417J 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 527882J 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 530717Bioorg 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 527556Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43.Acyclic cyanamide-based inhibitors of cathepsin K.
Ref 527556Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43.Acyclic cyanamide-based inhibitors of cathepsin K.
Ref 526417J 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 527872Bioorg 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 530459Antimicrob 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.
Ref 528643J 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 528643J 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 527885J Med Chem. 2005 Dec 1;48(24):7688-707.Interaction of papain-like cysteine proteases with dipeptide-derived nitriles.
Ref 536609The 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 527872Bioorg 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 528002J 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 528002J Med Chem. 2006 Feb 9;49(3):1066-79.Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K.

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