Structure-based discovery of a new class of Hsp90 inhibitors

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• 作者：Xavier Barril ; Paul Brough ; Martin Drysdale ; Roderick E. Hubbard ; Andrew Massey ; Allan Surgenor and Lisa Wright
• 关键词：Hsp90 inhibitor ; Docking ; Virtual screening ; Hit identification ; Phenol– ; naphthol ; Bis-phenol ; Structure-based drug discovery
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：15
• 期：23
• 页码：5187-5191
• 全文大小：264 K

文摘

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.