4HYH

X-RAY Crystal structure of compound 39 bound to human chk1 kinase domain

Summary for 4HYH

• Entry DOI: 10.2210/pdb4hyh/pdb
• Related: 4HYI
• Descriptor: Serine/threonine-protein kinase Chk1, 2-(6-methoxy-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-(piperazin-1-yl)pyridin-3-yl]-1,3-thiazole-4-carboxamide (3 entities in total)
• Functional Keywords: serine/threonine-protein kinase chk1 inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 33493.50

Authors

Fischmann, T.O. (deposition date: 2012-11-13, release date: 2013-03-06, Last modification date: 2024-02-28)

Primary citation

Huang, X.,Cheng, C.C.,Fischmann, T.O.,Duca, J.S.,Richards, M.,Tadikonda, P.K.,Reddy, P.A.,Zhao, L.,Arshad Siddiqui, M.,Parry, D.,Davis, N.,Seghezzi, W.,Wiswell, D.,Shipps, G.W.
Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors.
Bioorg.Med.Chem.Lett., 23:2590-2594, 2013

PubMed Abstract: Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported.

PubMed: 23535330
DOI: 10.1016/j.bmcl.2013.02.108

Experimental method

X-RAY DIFFRACTION (1.7 Å)