title: Identification and initial SAR of silybin: an Hsp90 inhibitor.
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.
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, KS 66045-7563, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhao
authors.forename: Gary E
authors.initials: GE
authors.lastname: Brandt
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Galam
authors.forename: Robert L
authors.initials: RL
authors.lastname: Matts
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
mesh_terms: D045744:Cell Line, Tumor; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D000077385:Silybin; D012838:Silymarin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D018841:HSP90 Heat-Shock Proteins; D012838:Silymarin; D000077385:Silybin