Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures

被引：61

作者：

Dymock, B ^{[1
]}

Barril, X ^{[1
]}

Beswick, M ^{[1
]}

Collier, A ^{[1
]}

Davies, N ^{[1
]}

Drysdale, M ^{[1
]}

Fink, A ^{[1
]}

Fromont, C ^{[1
]}

Hubbard, RE ^{[1
]}

Massey, A ^{[1
]}

Surgenor, A ^{[1
]}

Wright, L ^{[1
]}

机构：

[1] RiboTargets Ltd, Cambridge CB1 6GB, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 02期

关键词：

HSP90; chaperone; adenine inhibitors; HSP70; Raf-1;

D O I：

10.1016/j.bmcl.2003.11.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：325 / 328

页数：4

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