Structure-based discovery of a new class of Hsp90 inhibitors
Structure-based discovery of a new class of Hsp90 inhibitors
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DOI：
10.1016/j.bmcl.2005.08.092
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发表时间：
2005-12-01
影响因子：
2.7
通讯作者：
Wright, L
中科院分区：
文献类型：
--
作者：
Barril, X;Brough, P;Wright, L
基于对接的虚拟筛选将1-（2-苯酚）-2-萘酚化合物鉴定为一类新的低至亚微摩尔效力的Hsp 90抑制剂。在这里，我们报告的结合亲和力和细胞活动的几个成员这一类。最有效的化合物的高分辨率晶体结构揭示了其在Hsp 90的ATP结合位点中的结合模式，为所观察到的系列活性提供了理论基础，并提出了开发具有改进性质的化合物的策略。(c)2005爱思唯尔有限公司保留所有权利。
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.