2YWP

Crystal Structure of CHK1 with a Urea Inhibitor

「2FGA」から置き換えられました

2YWP の概要

• エントリーDOI: 10.2210/pdb2ywp/pdb
• 関連するPDBエントリー: 2AYP
• 分子名称: Serine/threonine-protein kinase Chk1, 1-(5-CHLORO-2,4-DIMETHOXYPHENYL)-3-(5-CYANOPYRAZIN-2-YL)UREA (2 entities in total)
• 機能のキーワード: protein-inhibitor complex, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O14757
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31402.47

構造登録者

Park, C. (登録日: 2007-04-21, 公開日: 2007-05-08, 最終更新日: 2024-03-13)

主引用文献

Li, G.,Hasvold, L.A.,Tao, Z.-F.,Wang, G.T.,Gwaltney II, S.L.,Patel, J.,Kovar, P.,Credo, R.B.,Chen, Z.,Zhang, H.,Park, C.,Sham, H.L.,Sowin, T.,Rosenberg, S.H.,Lin, N.-H.
Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors
Bioorg.Med.Chem.Lett., 16:2293-2298, 2006

PubMed Abstract: Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1) enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 microM) and enhanced doxorubicin cytotoxicity (IC50=0.44 microM) while displaying no single agent activity.

PubMed: 16446090
DOI: 10.1016/j.bmcl.2006.01.028

実験手法

X-RAY DIFFRACTION (2.9 Å)