1VSN

Crystal structure of a potent small molecule inhibitor bound to cathepsin K

Replaces:  2FDZ

Summary for 1VSN

• Entry DOI: 10.2210/pdb1vsn/pdb
• Descriptor: Cathepsin K, N-(2-AMINOETHYL)-N~2~-{(1S)-1-[4'-(AMINOSULFONYL)BIPHENYL-4-YL]-2,2,2-TRIFLUOROETHYL}-L-LEUCINAMIDE (3 entities in total)
• Functional Keywords: osteoporosis, structure-guided drug design, proteae, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 23517.27

Authors

McGrath, M. (deposition date: 2007-03-19, release date: 2007-04-24, Last modification date: 2024-10-16)

Primary citation

Li, C.S.,Deschenes, D.,Desmarais, S.,Falgueyret, J.P.,Gauthier, J.Y.,Kimmel, D.B.,McGrath, M.E.,McKay, D.J.,Percival, M.D.,Riendeau, D.,Rodan, S.B.,Truong, V.L.,Wesolowski, G.,Zamboni, R.,Black, W.C.
Identification of a potent and selective non-basic cathepsin K inhibitor.
Bioorg.Med.Chem.Lett., 16:1985-1989, 2006

PubMed Abstract: Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed excellent pharmacokinetics and efficacy in an ovariectomized (OVX) rhesus monkey model. The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors.

PubMed: 16413777
DOI: 10.1016/j.bmcl.2005.12.071

Experimental method

X-RAY DIFFRACTION (2 Å)