222036-17-1Relevant articles and documents
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): Design, synthesis, enzymatic activities, and X-ray crystallographic analysis
Bramson,Holmes,Hunter,Lackey,Lovejoy,Luzzio,Montana,Rocque,Rusnak,Shewchuk,Veal,Corona,Walker,Kuyper,Davis,Dickerson,Edelstein,Frye,Gampe Jr.,Harris,Hassell
, p. 4339 - 4358 (2007/10/03)
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 ～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.
