Identification of new Hsp90 inhibitors by structure-based virtual screening

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4839-42. doi: 10.1016/j.bmcl.2009.06.040. Epub 2009 Jun 13.

Abstract

Structure-based virtual screening identified pyrimidine-2,4,6-trione and 4H-1,2,4-triazole-3-thiol as novel scaffolds of Hsp90 ATPase inhibitors. Their binding modes in the ATP-binding pocket of Hsp90 were analyzed using AutoDoc program combined with molecular dynamics (MD) simulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cell Line, Tumor
  • Combinatorial Chemistry Techniques
  • Computer Simulation
  • Databases, Factual
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Pyrimidines / chemistry*
  • Receptor, ErbB-2 / metabolism
  • Triazoles / chemistry*

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Pyrimidines
  • Triazoles
  • 1,2,4-triazole
  • Receptor, ErbB-2