Mechanistic Studies of Sansalvamide A-Amide: An Allosteric Modulator of Hsp90

Herein, we show that sansalvarnide A-amide (San A-amide), a structurally unique molecule, influences a subset of cancer-related pathways involving heat shock protein 90 (Hsp90) We show that San A-amide specifically binds to the N-middle domain of Hsp90 and allosterically disrupts the binding of proteins thought to interact with the Hsp90 C-terminal domain, while having no effect on an N-terminal domain client protein This unique mechanism suggests that San A-amide is a potential tool for studying C-terminal binding proteins of Hsp90 as well as a promising lead in the development of new cancer therapeutics