2F7D
A mutant rabbit cathepsin K with a nitrile inhibitor
Summary for 2F7D
| Entry DOI | 10.2210/pdb2f7d/pdb |
| Descriptor | Cathepsin K, (1R,2R)-N-(2-AMINOETHYL)-2-{[(4-METHOXYPHENYL)SULFONYL]METHYL}CYCLOHEXANECARBOXAMIDE (3 entities in total) |
| Functional Keywords | papain cysteine protease, hydrolase |
| Biological source | Oryctolagus cuniculus (rabbit) |
| Cellular location | Lysosome : P43236 |
| Total number of polymer chains | 1 |
| Total formula weight | 23908.96 |
| Authors | Somoza, J.R. (deposition date: 2005-11-30, release date: 2006-03-07, Last modification date: 2024-11-06) |
| Primary citation | Crane, S.N.,Black, W.C.,Palmer, J.T.,Davis, D.E.,Setti, E.,Robichaud, J.,Paquet, J.,Oballa, R.M.,Bayly, C.I.,McKay, D.J.,Somoza, J.R.,Chauret, N.,Seto, C.,Scheigetz, J.,Wesolowski, G.,Masse, F.,Desmarais, S.,Ouellet, M. Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K. J.Med.Chem., 49:1066-1079, 2006 Cited by PubMed Abstract: A new series of nonpeptidic cathepsin K inhibitors that are based on a beta-substituted cyclohexanecarboxamide motif has been developed. Lead optimization yielded compounds with sub-nanomolar potency and exceptional selectivity profiles against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the cyclohexyl ring led to compounds with excellent pharmacokinetic properties. Considering the well-established role of cathepsin K in osteoclast-mediated bone turnover, compounds such as (-)-34a (hrab Cat K IC(50) 0.28 nM; >800-fold selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit great potential for development as an orally bioavailable therapeutic for treatment of diseases that involve bone loss. PubMed: 16451072DOI: 10.1021/jm051059p PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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