3KWB

Structure of CatK covalently bound to a dioxo-triazine inhibitor

Summary for 3KWB

• Entry DOI: 10.2210/pdb3kwb/pdb
• Related: 3KW9
• Descriptor: Cathepsin K, 3,5-dioxo-4-(3-piperidin-1-ylpropyl)-2-[3-(trifluoromethyl)phenyl]-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile (3 entities in total)
• Functional Keywords: covalent bond, cys 25, thioimidate, disease mutation, disulfide bond, glycoprotein, hydrolase, lysosome, protease, thiol protease, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 2
• Total formula weight: 47861.74

Authors

Uitdehaag, J.C.M.,van Zeeland, M. (deposition date: 2009-12-01, release date: 2010-04-07, Last modification date: 2024-11-06)

Primary citation

Rankovic, Z.,Cai, J.,Fradera, X.,Dempster, M.,Mistry, A.,Mitchell, A.,Long, C.,Hamilton, E.,King, A.,Boucharens, S.,Jamieson, C.,Gillespie, J.,Cumming, I.,Uitdehaag, J.,van Zeeland, M.
Dioxo-triazines as a novel series of cathepsin K inhibitors
Bioorg.Med.Chem.Lett., 20:1488-1490, 2010

PubMed Abstract: A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of 17nM against catK and >10,000nM in catL, catB and catS assays.

PubMed: 20153187
DOI: 10.1016/j.bmcl.2010.01.116

Experimental method

X-RAY DIFFRACTION (2.02 Å)