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Targeting the C-Terminus of Hsp90 as a Cancer Therapy

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 19)

Abstract

Classical Hsp90 inhibitors target the N-terminal ATP binding site. While these inhibitors have had some clinical success, treatment with these molecules leads to a dramatic increase in a set of stress-related proteins, a response that is referred to as a heat shock response. The induction of a heat shock response protects the cell against the protein aggregation induced by inhibiting Hsp90 and slows down cell death. Alternatively, inhibiting Hsp90 by modulating the C-terminus does not lead to a heat shock response. Current efforts to inhibit Hsp90’s C-terminus include molecules derived from natural products and mimics of native Hsp90-binding proteins. This diverse effort toward new C-terminal modulators of Hsp90 and their promising biological profile suggests that this strategy is likely the most productive future for targeting Hsp90.

Keywords

ATP binding inhibitors Cancer C-terminus Heat shock proteins Hsp90 Natural products Natural product small molecules 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.School of ChemistryUniversity of New South WalesKensingtonAustralia

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