| Literature DB >> 16843670 |
Keith W Woods1, John P Fischer, Akiyo Claiborne, Tongmei Li, Sheela A Thomas, Gui-Dong Zhu, Robert B Diebold, Xuesong Liu, Yan Shi, Vered Klinghofer, Edward K Han, Ran Guan, Shayna R Magnone, Eric F Johnson, Jennifer J Bouska, Amanda M Olson, Ron de Jong, Tilman Oltersdorf, Yan Luo, Saul H Rosenberg, Vincent L Giranda, Qun Li.
Abstract
A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (K(i)=0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of Akt activity. No selectivity amongst the Akt isoforms is observed for this analogue, but there is good selectivity against an panel of other kinases. It is least selective for other members of the AGC family of kinases but is nonetheless 40-fold selective for Akt over PKA. The compound shows cellular activity and significantly slows tumor growth in vivo.Entities:
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Year: 2006 PMID： 16843670 DOI： 10.1016/j.bmc.2006.06.047
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641