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

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• 作者：Mark T. Bilodeau ; Adrienne E. Balitza ; Jacob M. Hoffman ; Peter J. Manley ; Stanley F. Barnett ; Deborah Defeo-Jones ; Kathleen Haskell ; Raymond E. Jones ; Karen Le ; er ; Ronald G. Robinson ; Anthony M. Smith
• 关键词：Akt ; Oncology
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 June 2008
• 卷：18
• 期：11
• 页码：3178-3182
• 文件大小：146 K

摘要

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.