CHAPTER 10: Inhibitors of the Hsp90 C-terminus
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Published:23 Oct 2013
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Series: Drug Discovery Series
H. Zhao and B. S. J. Blagg, in Inhibitors of Molecular Chaperones as Therapeutic Agents, ed. T. D. Machajewski and Z. Gao, The Royal Society of Chemistry, 2013, pp. 259-301.
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Hsp90 is a promising therapeutic target for the treatment of cancer and neurodegenerative diseases. While current research focuses on drugging the N-terminal ATP-binding pocket, small molecules that disrupt the Hsp90 C-terminus manifest distinctive properties and may provide additional advantages over N-terminal inhibitors. Structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor identified, have led to a set of analogues that either induce a strong heat shock response or manifest potent anti-proliferative activities. The development of these novobiocin-based analogues and their biological evaluation is summarized in this chapter. Additional small molecules that bind the Hsp90 C-terminus are also discussed.