Identification of inhibitors of protein kinase B using fragment-based lead discovery

被引：124

作者：

Saxty, Gordon

Woodhead, Steven J.

Berdini, Valerio

Davies, Thomas G.

Verdonk, Marcel L.

Wyatt, Paul G.

Boyle, Robert G.

Barford, David

Downham, Robert

Garrett, Michelle D.

Carr, Robin A.

机构：

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

[2] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England

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

来源：

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

关键词：

D O I：

10.1021/jm070091b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80 mu M) was identified as a novel, low molecular weight inhibitor of protein kinase B (PKB). Herein we describe the rapid elaboration of highly potent and ligand efficient analogues using a fragment growing approach. Iterative structure-based design was supported by protein-ligand structure determinations using a PKA-PKB "chimera" and a final protein-ligand structure of a lead compound in PKB beta itself.

引用

页码：2293 / 2296

页数：4

共 24 条

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