| Literature DB >> 16644221 |
Gui-Dong Zhu1, Viraj B Gandhi, Jianchun Gong, Yan Luo, Xuesong Liu, Yan Shi, Ran Guan, Shayna R Magnone, Vered Klinghofer, Eric F Johnson, Jennifer Bouska, Alexander Shoemaker, Anatol Oleksijew, Ken Jarvis, Chang Park, Ron De Jong, Tilman Oltersdorf, Qun Li, Saul H Rosenberg, Vincent L Giranda.
Abstract
We describe a series of potent and selective oxindole-pyridine-based protein kinase B/Akt inhibitors. The most potent compound 11n in this series demonstrated an IC(50) of 0.17nM against Akt1 and more than 100-fold selectivity over other Akt isozymes. The selectivity against other protein kinases was highly dependent on the C-3 substitutions at the oxindole scaffold, with unsubstituted 9e or 3-furan-2-ylmethylene (11n) more selective and 3-(1H-pyrrol-2-yl)methylene (11f) or 3-(1H-imidazol-2-yl)methylene (11k) less selective. In a mouse xenograft model, 9d, 11f, and 11n inhibited tumor growth but with accompanying toxicity.Entities:
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Year: 2006 PMID： 16644221 DOI： 10.1016/j.bmcl.2006.04.005
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823