2HOG

crystal structure of Chek1 in complex with inhibitor 20

Summary for 2HOG

• Entry DOI: 10.2210/pdb2hog/pdb
• Descriptor: 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)
• Functional Keywords: chek1, kinase, cell cycle checkpoint, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 37218.46

Authors

Yan, Y.,Ikuta, M. (deposition date: 2006-07-14, release date: 2007-04-24, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)