3KX1

Cathepsin K in complex with a selective 2-cyano-pyrimidine inhibitor

Summary for 3KX1

• Entry DOI: 10.2210/pdb3kx1/pdb
• Related: 3KWZ
• Descriptor: Cathepsin K, 4-cycloheptyl-6-(3-piperidin-1-ylpropyl)pyrimidine-2-carbonitrile, SULFATE ION, ... (4 entities in total)
• Functional Keywords: cathepsin k, enzyme inhibitor, covalent reversible inhibitor, 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: 1
• Total formula weight: 24042.08

Authors

Fradera, X.,Uitdehaag, J.C.M.,van Zeeland, M. (deposition date: 2009-12-02, release date: 2010-03-02, Last modification date: 2024-10-30)

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 (1.51 Å)