2HOG

crystal structure of Chek1 in complex with inhibitor 20

2HOG の概要

• エントリーDOI: 10.2210/pdb2hog/pdb
• 分子名称: Serine/threonine-protein kinase Chk1, (5-{3-[5-(PIPERIDIN-1-YLMETHYL)-1H-INDOL-2-YL]-1H-INDAZOL-6-YL}-2H-1,2,3-TRIAZOL-4-YL)METHANOL (3 entities in total)
• 機能のキーワード: chek1, kinase, cell cycle checkpoint, 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: 37218.46

構造登録者

Yan, Y.,Ikuta, M. (登録日: 2006-07-14, 公開日: 2007-04-24, 最終更新日: 2023-08-30)

主引用文献

Fraley, M.E.,Steen, J.T.,Brnardic, E.J.,Arrington, K.L.,Spencer, K.L.,Hanney, B.A.,Kim, Y.,Hartman, G.D.,Stirdivant, S.M.,Drakas, B.A.,Rickert, K.,Walsh, E.S.,Hamilton, K.,Buser, C.A.,Hardwick, J.,Tao, W.,Beck, S.C.,Mao, X.,Lobell, R.B.,Sepp-Lorenzino, L.,Yan, Y.,Ikuta, M.,Munshi, S.K.,Kuo, L.C.,Kreatsoulas, C.
3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6.
Bioorg.Med.Chem.Lett., 16:6049-6053, 2006

PubMed Abstract: The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is described. Introduction of amides and heteroaryl groups at the C6 position of the indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7 to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft.

PubMed: 16978863
DOI: 10.1016/j.bmcl.2006.08.118

実験手法

X-RAY DIFFRACTION (1.9 Å)