2. Academic Validation
  3. Structure-based discovery of a new class of Hsp90 inhibitors

Structure-based discovery of a new class of Hsp90 inhibitors

  • Bioorg Med Chem Lett. 2005 Dec 1;15(23):5187-91. doi: 10.1016/j.bmcl.2005.08.092.
Xavier Barril 1,  Paul Brough,  Martin Drysdale,  Roderick E Hubbard,  Andrew Massey,  Allan Surgenor,  Lisa Wright
Affiliations

Affiliation

PMID: 16202589 DOI: 10.1016/j.bmcl.2005.08.092
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.

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