A systematic protocol for the characterization of Hsp90 modulators

Bioorg Med Chem. 2011 Jan 1;19(1):684-92. doi: 10.1016/j.bmc.2010.10.029. Epub 2010 Oct 19.

Abstract

Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones / pharmacology
  • Cell Line, Tumor
  • Chromatography, Affinity
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / drug effects*
  • Humans
  • Hydrolysis
  • Immunoprecipitation
  • Lactams, Macrocyclic / pharmacology
  • Models, Molecular
  • Novobiocin / pharmacology
  • Triterpenes / pharmacology

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Triterpenes
  • Novobiocin
  • tripterine
  • geldanamycin