1ke6
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(New page: 200px<br /> <applet load="1ke6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ke6, resolution 2.0Å" /> '''CYCLIN-DEPENDENT KIN...)
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Revision as of 15:43, 12 November 2007
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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
Overview
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.
About this Structure
1KE6 is a Single protein structure of sequence from Homo sapiens with LS2 as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis., Bramson HN, Corona J, Davis ST, Dickerson SH, Edelstein M, Frye SV, Gampe RT Jr, Harris PA, Hassell A, Holmes WD, Hunter RN, Lackey KE, Lovejoy B, Luzzio MJ, Montana V, Rocque WJ, Rusnak D, Shewchuk L, Veal JM, Walker DH, Kuyper LF, J Med Chem. 2001 Dec 6;44(25):4339-58. PMID:11728181
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