3V8S

Human RHO-ASSOCIATED PROTEIN KINASE 1 (ROCK 1) IN COMPLEX WITH INDAZOLE DERIVATIVE (COMPOUND 18)

3V8S の概要

• エントリーDOI: 10.2210/pdb3v8s/pdb
• 分子名称: Rho-associated protein kinase 1, 1-(1H-indazol-5-yl)-3-(2-phenylethyl)urea (3 entities in total)
• 機能のキーワード: kinase, dimerization, myosin, transferase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q13464
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 191063.94

構造登録者

Martin, M.P.,Zhu, J.-Yi.,Schonbrunn, E. (登録日: 2011-12-23, 公開日: 2012-02-08, 最終更新日: 2023-09-13)

主引用文献

Li, R.,Martin, M.P.,Liu, Y.,Wang, B.,Patel, R.A.,Zhu, J.Y.,Sun, N.,Pireddu, R.,Lawrence, N.J.,Li, J.,Haura, E.B.,Sung, S.S.,Guida, W.C.,Schonbrunn, E.,Sebti, S.M.
Fragment-based and structure-guided discovery and optimization of rho kinase inhibitors.
J.Med.Chem., 55:2474-2478, 2012

PubMed Abstract: Using high concentration biochemical assays and fragment-based screening assisted by structure-guided design, we discovered a novel class of Rho-kinase inhibitors. Compound 18 was equipotent for ROCK1 (IC(50) = 650 nM) and ROCK2 (IC(50) = 670 nM), whereas compound 24 was more selective for ROCK2 (IC(50) = 100 nM) over ROCK1 (IC(50) = 1690 nM). The crystal structure of the compound 18-ROCK1 complex revealed that 18 is a type 1 inhibitor that binds the hinge region in the ATP binding site. Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells.

PubMed: 22272748
DOI: 10.1021/jm201289r

実験手法

X-RAY DIFFRACTION (2.286 Å)