Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors

  • Bioorg Med Chem Lett. 2005 Feb 1;15(3):761-4. doi: 10.1016/j.bmcl.2004.11.011.
Craig W Lindsley  1 ,  Zhijian Zhao ,  William H Leister ,  Ronald G Robinson ,  Stanley F Barnett ,  Deborah Defeo-Jones ,  Raymond E Jones ,  George D Hartman ,  Joel R Huff ,  Hans E Huber ,  Mark E Duggan
Affiliations
  • 1. Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, Merck and Co., PO Box 4, West Point, PA 19486, USA. [email protected]
PMID: 15664853 DOI: 10.1016/j.bmcl.2004.11.011
Abstract

This letter describes the development of two series of potent and selective allosteric Akt kinase inhibitors that display an unprecedented level of selectivity for either Akt1, Akt2 or both Akt1/Akt2. An iterative analog library synthesis approach quickly provided a highly selective Akt1/Akt2 Inhibitor that induces Apoptosis in tumor cells and inhibits Akt phosphorylation in vivo.

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