Identification and initial SAR of silybin: an Hsp90 inhibitor

Bioorg Med Chem Lett. 2011 May 1;21(9):2659-64. doi: 10.1016/j.bmcl.2010.12.088. Epub 2010 Dec 28.

Abstract

Through Hsp90-dependent firefly luciferase refolding and Hsp90-dependent heme-regulated eIF2α kinase (HRI) activation assays, silybin was identified as a novel Hsp90 inhibitor. Subsequently, a library of silybin analogues was designed, synthesized and evaluated. Initial SAR studies identified the essential, non-essential and detrimental functionalities on silybin that contribute to Hsp90 inhibition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Drug Design*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Molecular Structure
  • Silybin
  • Silymarin / chemical synthesis
  • Silymarin / chemistry*
  • Silymarin / pharmacology*
  • Structure-Activity Relationship

Substances

  • HSP90 Heat-Shock Proteins
  • Silymarin
  • Silybin