1ke9: Difference between revisions

[[Image:1ke9.gif|left|200px]]<br /><applet load="1ke9" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1KE9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=LS5:'>LS5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KE9 OCA].  

[[Category: Bramson, H N.]]

[[Category: Davis, S T.]]

[[Category: Dickerson, S H.]]

[[Category: Frye, S V.]]

[[Category: Gampe, R T.]]

[[Category: Hassell, A M.]]

[[Category: Kuyper, L F.]]

[[Category: Shewchuk, L M.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:09 2008''