3KW9

X-ray structure of Cathepsin K covalently bound to a triazine ligand

Summary for 3KW9

• Entry DOI: 10.2210/pdb3kw9/pdb
• Related: 3KWB
• Descriptor: Cathepsin K, 4-(cyclohexylamino)-6-piperazin-1-yl-1,3,5-triazine-2-carbonitrile, trifluoroacetic acid, ... (4 entities in total)
• Functional Keywords: cysteine, thioimidate, disulfide bond, cys protease, inhibitor, non-peptide, hydrolase, protease, thiol protease, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 1
• Total formula weight: 23924.87

Authors

Uitdehaag, J.C.M.,van Zeeland, M. (deposition date: 2009-12-01, release date: 2010-03-02, Last modification date: 2024-11-06)

Primary citation

Rankovic, Z.,Cai, J.,Kerr, J.,Fradera, X.,Robinson, J.,Mistry, A.,Hamilton, E.,McGarry, G.,Andrews, F.,Caulfield, W.,Cumming, I.,Dempster, M.,Waller, J.,Scullion, P.,Martin, I.,Mitchell, A.,Long, C.,Baugh, M.,Westwood, P.,Kinghorn, E.,Bruin, J.,Hamilton, W.,Uitdehaag, J.,van Zeeland, M.,Potin, D.,Saniere, L.,Fouquet, A.,Chevallier, F.,Deronzier, H.,Dorleans, C.,Nicolai, E.
Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors.
Bioorg.Med.Chem.Lett., 20:1524-1527, 2010

PubMed Abstract: Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC(50)=4nM), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.

PubMed: 20149657
DOI: 10.1016/j.bmcl.2010.01.100

Experimental method

X-RAY DIFFRACTION (1.8 Å)