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Identification and initial SAR of silybin: an Hsp90 inhibitor
Huiping Zhao1, Gary E Brandt, Lakshmi Galam
1Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, KS 66045-7563, USA.
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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