2E9N

Structure of h-CHK1 complexed with A767085

2E9N の概要

• エントリーDOI: 10.2210/pdb2e9n/pdb
• 関連するPDBエントリー: 2AYP 2E9O 2E9P 2E9U 2E9V 2FGA 2GHG
• 分子名称: Serine/threonine-protein kinase Chk1, 3-(4'-HYDROXYBIPHENYL-4-YL)-N-(4-HYDROXYCYCLOHEXYL)-1,4-DIHYDROINDENO[1,2-C]PYRAZOLE-6-CARBOXAMIDE (3 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: 31534.28

構造登録者

Park, C. (登録日: 2007-01-26, 公開日: 2008-01-29, 最終更新日: 2024-03-13)

主引用文献

Tong, Y.,Claiborne, A.,Stewart, K.D.,Park, C.,Kovar, P.,Chen, Z.,Credo, R.B.,Gu, W.Z.,Gwaltney, S.L.,Judge, R.A.,Zhang, H.,Rosenberg, S.H.,Sham, H.L.,Sowin, T.J.,Lin, N.H.
Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors.
Bioorg.Med.Chem., 15:2759-2767, 2007

PubMed Abstract: A new class of checkpoint kinase 1 (CHK-1) inhibitors bearing a 1,4-dihydroindeno[1,2-c]pyrazole core was developed after initial hits from high throughput screening. The efficient hit-to-lead process was facilitated by X-ray crystallography and led to potent inhibitors (<10nM) against CHK-1. X-ray co-crystal structures of bound inhibitors demonstrated that two sub-series of this class of compounds, exemplified by 21 and 41, exhibit distinctive hydrogen bonding patterns in the specificity pocket of the active site. Two compounds, 41 and 43, were capable of potentiating doxorubicin and camptothecin, both DNA-damaging agents, in cell proliferation assays (MTS and soft agar assays) and abrogating G2/M checkpoint in a mechanism-based FACS assay.

PubMed: 17287122
DOI: 10.1016/j.bmc.2007.01.012

実験手法

X-RAY DIFFRACTION (2.5 Å)