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. Epub 2005 Oct 3.

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.

Publication types

  • Comparative Study

MeSH terms

  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Molecular Structure
  • Naphthols / chemistry*
  • Naphthols / pharmacology*

Substances

  • HSP90 Heat-Shock Proteins
  • Naphthols

Associated data

  • PDB/2BZ5