| Literature DB >> 16249095 |
Ian Collins1, John Caldwell, Tatiana Fonseca, Alastair Donald, Vassilios Bavetsias, Lisa-Jane K Hunter, Michelle D Garrett, Martin G Rowlands, G Wynne Aherne, Thomas G Davies, Valerio Berdini, Steven J Woodhead, Deborah Davis, Lisa C A Seavers, Paul G Wyatt, Paul Workman, Edward McDonald.
Abstract
Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3beta phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.Entities:
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Year: 2005 PMID： 16249095 DOI： 10.1016/j.bmc.2005.09.055
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641