Target Validation Information
TTD ID T11388
Target Name Cathepsin K (CTSK)
Type of Target
Clinical trial
Drug Potency against Target Odanacatib Drug Info IC50 = 0.2 nM [14]
Relacatib Drug Info Ki = 0.75 nM
(S)-1-benzylcyclopentyl 1-oxohexan-2-ylcarbamate Drug Info IC50 = 0.35 nM [4]
(S)-tert-butyl 1-oxohexan-2-ylcarbamate Drug Info IC50 = 51 nM [4]
(S)-tert-butyl 4-methyl-1-oxopentan-2-ylcarbamate Drug Info IC50 = 31 nM [4]
2-cyclohexylamino-pyridine-2-carbonitrile Drug Info IC50 = 1000 nM [8]
2-cyclohexylamino-pyrimidine-4-carbonitrile Drug Info IC50 = 120 nM [8]
4-cycloheptyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 84 nM [12]
4-cyclohexyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 680 nM [12]
4-cyclohexylamino-pyrimidine-2-carbonitrile Drug Info IC50 = 170 nM [8]
4-cyclooctyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 11 nM [12]
4-phenyl-6-propylpyrimidine-2-carbonitrile Drug Info IC50 = 1122 nM [13]
4-propyl-6-m-tolylpyrimidine-2-carbonitrile Drug Info IC50 = 182 nM [13]
Boc-Agly-Val-Agly-OEt Drug Info Ki = 61 nM [1]
BOCEPREVIR Drug Info IC50 = 40 nM [11]
GNF-PF-5434 Drug Info Ki = 1.2 nM [9]
L-006235-1 Drug Info IC50 = 0.5 nM [5]
L-873724 Drug Info IC50 = 6.1 nM [10]
L-873724 Drug Info IC50 = 0.8 nM [14]
N-(1-((cyanomethyl)carbamoyl)cyclohexyl)benzamide Drug Info IC50 = 78 nM [7]
N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile Drug Info Ki = 300 nM [6]
N-(benzyloxycarbonyl)-leucyl-glycine-nitrile Drug Info Ki = 35 nM [6]
N-(cyanomethyl)cyclohex-1-ene-1-carboxamide Drug Info IC50 = 3400 nM [7]
N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile Drug Info Ki = 5800 nM [6]
N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile Drug Info Ki = 120 nM [6]
N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile Drug Info Ki = 730 nM [6]
N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile Drug Info Ki = 1270 nM [6]
N-(tert-butoxycarbonyl)-norvalyl-glycine-nitrile Drug Info Ki = 1100 nM [6]
N-(tert-butoxycarbonyl)-valyl-glycine-nitrile Drug Info Ki = 6500 nM [6]
N-acetyl-phenylalanyl-glycine-nitrile Drug Info Ki = 7500 nM [6]
N-benzoyl-phenylalanyl-glycine-nitrile Drug Info Ki = 1500 nM [6]
P2,P3 Ketoamide derivative Drug Info IC50 = 40 nM [2]
Pyrrolidine-1-carbonitrile Drug Info Ki = 2100 nM [3]
Tert-butyl (2S)-1-cyanopyrrolidine-2-carboxylate Drug Info Ki = 60 nM [3]
Z-Ala-Leu-His-Agly-Ile-Val-OMe Drug Info Ki = 0.86 nM [1]
Z-Ala-Leu-lle-Agly-Ile-Val-NHBzl Drug Info Ki = 2.45 nM [1]
Z-Ala-Leu-lle-Agly-Ile-Val-OMe Drug Info Ki = 2.12 nM [1]
Z-Ala-Leu-Nal-Agly-Ile-Val-OMe Drug Info Ki = 5.75 nM [1]
Z-Ala-Leu-Phe-Agly-Ile-Val-OMe Drug Info Ki = 0.18 nM [1]
Z-Ala-Leu-Tyr(Me)-Agly-Ile-Val-OMe Drug Info Ki = 8.42 nM [1]
Z-Arg-Leu-Val-Agly-Ala-Gly-NH2 Drug Info Ki = 6.76 nM [1]
Z-Arg-Leu-Val-Agly-Ile-Val-Trp-NH2 Drug Info Ki = 72 nM [1]
Z-Arg-Leu-Val-Agly-Ileu-Val-OMe Drug Info Ki = 21 nM [1]
Z-Arg-Leu-Val-Agly-Trp-Val-Ala-NH2 Drug Info Ki = 100 nM [1]
Z-Arg-Leu-Val-Agly-Val-Ala-NH2 Drug Info Ki = 2.13 nM [1]
Z-leu-Val-Agly-Val-OBzl Drug Info Ki = 34 nM [1]
Action against Disease Model Odanacatib Drug Info 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. [15]
References
REF 1 Azapeptides structurally based upon inhibitory sites of cystatins as potent and selective inhibitors of cysteine proteases. J Med Chem. 2002 Sep 12;45(19):4202-11.
REF 2 Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4897-902.
REF 3 Acyclic cyanamide-based inhibitors of cathepsin K. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3039-43.
REF 4 Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83.
REF 5 Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional se... J Med Chem. 2005 Dec 1;48(24):7535-43.
REF 6 Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. J Med Chem. 2005 Dec 1;48(24):7688-707.
REF 7 Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K. J Med Chem. 2006 Feb 9;49(3):1066-79.
REF 8 2-Cyano-pyrimidines: a new chemotype for inhibitors of the cysteine protease cathepsin K. J Med Chem. 2007 Feb 22;50(4):591-4.
REF 9 Substrate optimization for monitoring cathepsin C activity in live cells. Bioorg Med Chem. 2009 Feb 1;17(3):1064-70.
REF 10 Identification of a nonbasic, nitrile-containing cathepsin K inhibitor (MK-1256) that is efficacious in a monkey model of osteoporosis. J Med Chem. 2008 Oct 23;51(20):6410-20.
REF 11 MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease. Antimicrob Agents Chemother. 2010 Jan;54(1):305-11.
REF 12 Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1524-7.
REF 13 2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4447-50.
REF 14 The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8.
REF 15 Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol Chem. 2009 Sep;390(9):941-8.

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