Structure-based discovery of a new class of Hsp90 inhibitors

被引：73

作者：

Barril, X ^{[1
]}

Brough, P ^{[1
]}

Drysdale, M ^{[1
]}

Hubbard, RE ^{[1
]}

Massey, A ^{[1
]}

Surgenor, A ^{[1
]}

Wright, L ^{[1
]}

机构：

[1] Vernalis R&D Ltd, Cambridge CB1 6GB, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 23期

关键词：

Hsp90; inhibitor; docking; virtual screening; hit identification; phenol-naphthol; bis-phenol; structure-based drug discovery;

D O I：

10.1016/j.bmcl.2005.08.092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Docking-based virtual screening identified 1-(2-phenol)-2-naphthol compounds as a new class of Hsp90 inhibitors of low to sub-micromolar potency. Here we report the binding affinities and cellular activities of several members of this class. A high resolution crystal structure of the most potent compound reveals its binding mode in the ATP binding site of Hsp90, providing a rationale for the observed activity of the series and suggesting strategies for developing compounds with improved properties. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：5187 / 5191

页数：5

共 30 条

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