3NCZ

X-Ray Co-structure of Rho-Associated Protein Kinase (ROCK1) with a potent 2H-isoquinolin-1-one inhibitor

3NCZ の概要

• エントリーDOI: 10.2210/pdb3ncz/pdb
• 関連するPDBエントリー: 3NDM
• 分子名称: Rho-associated protein kinase 1, cis-4-amino-N-(7-chloro-1-oxo-1,2-dihydroisoquinolin-6-yl)cyclohexanecarboxamide (3 entities in total)
• 機能のキーワード: rho kinase, dimer, phosphorylation, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 193328.28

構造登録者

Li, X. (登録日: 2010-06-06, 公開日: 2010-12-08, 最終更新日: 2024-02-21)

主引用文献

Ginn, J.D.,Bosanac, T.,Chen, R.,Cywin, C.,Hickey, E.,Kashem, M.,Kerr, S.,Kugler, S.,Li, X.,Prokopowicz, A.,Schlyer, S.,Smith, J.D.,Turner, M.R.,Wu, F.,Young, E.R.
Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: Part 2, optimization for blood pressure reduction in spontaneously hypertensive rats.
Bioorg.Med.Chem.Lett., 20:5153-5156, 2010

PubMed Abstract: Phenylglycine substituted isoquinolones 1 and 2 have previously been described as potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this series to improve metabolic stability and rat oral exposure. Piperidine analog 20 which demonstrates sustained blood pressure normalization in an SHR blood pressure reduction model was identified through this effort.

PubMed: 20678931
DOI: 10.1016/j.bmcl.2010.07.014

実験手法

X-RAY DIFFRACTION (3 Å)