2. Academic Validation
  3. Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model

Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model

  • Bioorg Med Chem Lett. 2008 Jun 1;18(11):3178-82. doi: 10.1016/j.bmcl.2008.04.074.
Mark T Bilodeau 1,  Adrienne E Balitza,  Jacob M Hoffman,  Peter J Manley,  Stanley F Barnett,  Deborah Defeo-Jones,  Kathleen Haskell,  Raymond E Jones,  Karen Leander,  Ronald G Robinson,  Anthony M Smith,  Hans E Huber,  George D Hartman
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., PO Box 4, West Point, PA 19486 USA. [email protected]
PMID: 18479914 DOI: 10.1016/j.bmcl.2008.04.074
Abstract

A series of naphthyridine and naphthyridinone allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been optimized to have potent dual activity against the activated kinase as well as the activation of Akt in cells. One molecule in particular, compound 17, has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model.

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