Rapid evolution of 6-phenylpurine inhibitors of protein kinase B through structure-based design

被引：57

作者：

Donald, Alastair

McHardy, Tatiana

Rowlands, Martin G.

Hunter, Lisa-Jane K.

Davies, Thomas G.

Berdini, Valerio

Boyle, Robert G.

Aherne, G. Wynne

Garrett, Michelle D.

Collins, Ian

机构：

[1] Inst Canc Res, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England

[2] Astex Therapeut Ltd, Cambridge CB4 0QA, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 10期

关键词：

D O I：

10.1021/jm0700924

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

6-Phenylpurines were identified as novel, ATP-competitive inhibitors of protein kinase B (PKB/Akt) from a fragment-based screen and were rapidly progressed to potent compounds using iterative protein - ligand crystallography with a PKA-PKB chimeric protein. An elaborated lead compound showed cell growth inhibition and effects on cellular signaling pathways characteristic of PKB inhibition.

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收藏

页码：2289 / 2292

页数：4

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