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ACS Med Chem Lett. 2010 Jan 1;1(1):4-8.

Mechanistic studies of Sansalvamide A-amide: an allosteric modulator of Hsp90.

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1
Department of Chemistry and Biochemistry, 5500 Campanile Road, San Diego State University, San Diego, CA 92182-1030.

Abstract

Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 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.

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