| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T68290 | ||||
| Target Name | Cathepsin S (CTSS) | ||||
| Type of Target |
Clinical trial |
||||
| Drug Potency against Target | CRA-028129 | Drug Info | IC50 = 30~100 nM | ||
| 4-cycloheptyl-6-propylpyrimidine-2-carbonitrile | Drug Info | IC50 = 1300 nM | [8] | ||
| 4-cyclooctyl-6-propylpyrimidine-2-carbonitrile | Drug Info | IC50 = 2239 nM | [8] | ||
| 4-propyl-6-m-tolylpyrimidine-2-carbonitrile | Drug Info | IC50 = 950 nM | [10] | ||
| 6-(3-(trifluoromethyl)phenyl)picolinonitrile | Drug Info | IC50 = 2884 nM | [9] | ||
| Ac-hPhe-Leu-Ala-LeuVSMe | Drug Info | IC50 = 6900 nM | [4] | ||
| Ac-hPhe-Leu-Gly-LeuVSMe | Drug Info | IC50 = 12000 nM | [4] | ||
| Ac-hPhe-Leu-Phe-LeuVSMe | Drug Info | IC50 = 150 nM | [4] | ||
| BOCEPREVIR | Drug Info | IC50 = 120 nM | [7] | ||
| Cbz-Glu(OtBu)-Ala-LeuVSMe | Drug Info | IC50 = 3000 nM | [4] | ||
| Cbz-Ile-hPhe-Ala-LeuVSMe | Drug Info | IC50 = 10000 nM | [4] | ||
| Cbz-Ile-Leu-Ala-LeuVSMe | Drug Info | IC50 = 700 nM | [4] | ||
| Cbz-Ile-MetO2-Ala-LeuVSMe | Drug Info | IC50 = 13000 nM | [4] | ||
| Cbz-Ile-Phe-Ala-LeuVSMe | Drug Info | IC50 = 9000 nM | [4] | ||
| Cbz-Ile-Pro-Ala-LeuVSMe | Drug Info | IC50 = 13000 nM | [4] | ||
| Cbz-Ile-t-ButylGln-Ala-LeuVSMe | Drug Info | IC50 = 3300 nM | [4] | ||
| Cbz-Ile-t-ButylhomoGlu-Ala-LeuVSMe | Drug Info | IC50 = 7100 nM | [4] | ||
| GNF-PF-5434 | Drug Info | Ki < 0.1 nM | [6] | ||
| L-006235-1 | Drug Info | IC50 = 318 nM | [2] | ||
| L-873724 | Drug Info | IC50 = 2441 nM | [5] | ||
| N-(1-oxobutan-2-yl)-3-(trifluoromethyl)benzamide | Drug Info | IC50 = 1070 nM | [11] | ||
| N-(2-naphthylsulfonyl)-glycyl-glycine-nitrile | Drug Info | Ki = 2500 nM | [3] | ||
| N-(4-phenylbenzoyl)-phenylalanyl-glycine-nitrile | Drug Info | Ki = 240 nM | [3] | ||
| N-(benzyloxycarbonyl)-leucyl-glycine-nitrile | Drug Info | Ki = 130 nM | [3] | ||
| N-(tert-butoxycarbonyl)-isoleucyl-glycine-nitrile | Drug Info | Ki = 4100 nM | [3] | ||
| N-(tert-butoxycarbonyl)-leucyl-glycine-nitrile | Drug Info | Ki = 130 nM | [3] | ||
| N-(tert-butoxycarbonyl)-methionyl-glycine-nitrile | Drug Info | Ki = 660 nM | [3] | ||
| N-(tert-butoxycarbonyl)-norleucyl-glycine-nitrile | Drug Info | Ki = 550 nM | [3] | ||
| N-(tert-butoxycarbonyl)-norvalyl-glycine-nitrile | Drug Info | Ki = 900 nM | [3] | ||
| N-(tert-butoxycarbonyl)-tyrosyl-glycine-nitrile | Drug Info | Ki = 970 nM | [3] | ||
| N-(tert-butoxycarbonyl)-valyl-glycine-nitrile | Drug Info | Ki = 6200 nM | [3] | ||
| N-acetyl-phenylalanyl-glycine-nitrile | Drug Info | Ki = 1400 nM | [3] | ||
| N-benzoyl-phenylalanyl-glycine-nitrile | Drug Info | Ki = 77 nM | [3] | ||
| P2,P3 Ketoamide derivative | Drug Info | IC50 = 130 nM | [1] | ||
| Action against Disease Model | CRA-028129 | Drug Info | CRA-028129, a pico molar Cat S inhibitor, has nano molar activity in a cellular assay | [12] | |
| References | |||||
| REF 1 | 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 2 | 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 3 | Interaction of papain-like cysteine proteases with dipeptide-derived nitriles. J Med Chem. 2005 Dec 1;48(24):7688-707. | ||||
| REF 4 | 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 c... J Med Chem. 2006 May 18;49(10):2953-68. | ||||
| REF 5 | The identification of potent, selective, and bioavailable cathepsin S inhibitors. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4929-33. | ||||
| REF 6 | Substrate optimization for monitoring cathepsin C activity in live cells. Bioorg Med Chem. 2009 Feb 1;17(3):1064-70. | ||||
| REF 7 | MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease. Antimicrob Agents Chemother. 2010 Jan;54(1):305-11. | ||||
| REF 8 | 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 9 | 4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4507-10. | ||||
| REF 10 | 2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4447-50. | ||||
| REF 11 | Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. | ||||
| REF 12 | Prostaglandin receptor signaling in disease. ScientificWorldJournal. 2007 Sep 1;7:1329-47. | ||||
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