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.
Huiping Zhao  1 ,  Gary E Brandt ,  Lakshmi Galam ,  Robert L Matts ,  Brian S J Blagg
Affiliations
  • 1. Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, KS 66045-7563, USA.
PMID: 21273068 DOI: 10.1016/j.bmcl.2010.12.088
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.

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