1TU6

Cathepsin K complexed with a ketoamide inhibitor

1TU6 の概要

• エントリーDOI: 10.2210/pdb1tu6/pdb
• 分子名称: Cathepsin K, SULFATE ION, [1-(4-FLUOROBENZYL)CYCLOBUTYL]METHYL (1S)-1-[OXO(1H-PYRAZOL-5-YLAMINO)ACETYL]PENTYLCARBAMATE, ... (4 entities in total)
• 機能のキーワード: catk, cysteine protease, hydrolase
• 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: 2
• 化学式量合計: 48224.15

構造登録者

Barrett, D.G.,Catalano, J.G.,Deaton, D.N.,Hassell, A.M.,Long, S.T.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M.,Wells-Knecht, K.J.,Wright, L.L. (登録日: 2004-06-24, 公開日: 2004-09-21, 最終更新日: 2024-11-20)

主引用文献

Barrett, D.G.,Catalano, J.G.,Deaton, D.N.,Hassell, A.M.,Long, S.T.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M.,Wells-Knecht, K.J.,Willard, D.H.,Wright, L.L.
Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with improved pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions
BIOORG.MED.CHEM.LETT., 14:4897-4902, 2004

PubMed Abstract: A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors.

PubMed: 15341947
DOI: 10.1016/j.bmcl.2004.07.031

実験手法

X-RAY DIFFRACTION (1.75 Å)