3KW9

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

3KW9 の概要

• エントリーDOI: 10.2210/pdb3kw9/pdb
• 関連するPDBエントリー: 3KWB
• 分子名称: Cathepsin K, 4-(cyclohexylamino)-6-piperazin-1-yl-1,3,5-triazine-2-carbonitrile, trifluoroacetic acid, ... (4 entities in total)
• 機能のキーワード: cysteine, thioimidate, disulfide bond, cys protease, inhibitor, non-peptide, hydrolase, protease, thiol protease, zymogen
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Lysosome: P43235
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23924.87

構造登録者

Uitdehaag, J.C.M.,van Zeeland, M. (登録日: 2009-12-01, 公開日: 2010-03-02, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)