1KE6: CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH N-METHYL-{4-[2-(7-OXO-6,7-DIHYDRO-8H-[1,3]THIAZOLO[5,4-E]INDOL-8-YLIDENE)HYDRAZINO]PHENYL}METHANESULFONAMIDE

Citation:
Abstract
Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.
PDB ID: 1KE6Download
MMDB ID: 19535
PDB Deposition Date: 2001/11/14
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1KE6: monomeric; determined by author
Molecular Components in 1KE6
Label Count Molecule
Protein (1 molecule)
1
Cell Division Protein Kinase 2(Gene symbol: CDK2)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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