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ID: ALA1141210

Journal: Bioorg Med Chem Lett

Title: Structure-based discovery of a new class of Hsp90 inhibitors.

Authors: Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L.

Abstract: 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.

CiteXplore: 16202589

DOI: 10.1016/j.bmcl.2005.08.092