Rapid Evolution of 6-Phenylpurine Inhibitors of Protein Kinase B through Structure-Based Design
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- 作者：Alastair Donald ; Tatiana McHardy ; Martin G. Rowlands ; Lisa-Jane K. Hunter ; Thomas G. Davies ; Valerio Berdini ; Robert G. Boyle ; G. Wynne Aherne ; Michelle D. Garrett ; Ian Collins
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：May 17, 2007
- 年：2007
- 卷：50
- 期：10
- 页码：2289 - 2292
- 全文大小：252K
- 年卷期：v.50,no.10(May 17, 2007)
- ISSN：1520-4804
文摘
6-Phenylpurines were identified as novel, ATP-competitiveinhibitors of protein kinase B (PKB/Akt) from a fragment-based screenand were rapidly progressed to potent compounds using iterativeprotein-ligand crystallography with a PKA-PKB chimeric protein.An elaborated lead compound showed cell growth inhibition and effectson cellular signaling pathways characteristic of PKB inhibition.