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Bioorg Med Chem. 2006 Feb 15;14(4):1255-73. Epub 2005 Oct 24.

Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B.

Author information

1
Cancer Research, UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey. Ian.Collins@icr.ac.uk

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.

PMID:
16249095
DOI:
10.1016/j.bmc.2005.09.055
[Indexed for MEDLINE]

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