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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Paralog Specific Hsp90 Inhibitors – A Brief History and a Bright Future

Author(s): Daniel T. Gewirth

Volume 16, Issue 25, 2016

Page: [2779 - 2791] Pages: 13

DOI: 10.2174/1568026616666160413141154

Price: $65

Abstract

Background. The high sequence and structural homology among the hsp90 paralogs – Hsp90α, Hsp90β, Grp94, and Trap-1 – has made the development of paralog-specific inhibitors a challenging proposition.

Objective. This review surveys the state of developments in structural analysis, compound screening, and structure-based design that have been brought to bear on this problem.

Results. First generation compounds that selectively bind to Hsp90, Grp94, or Trap-1 have been identified.

Conclusion. With the proof of principle firmly established, the prospects for further progress are bright.

Keywords: Hsp90, Grp94, Trap-1, Paralog-selective inhibitor, Structure-based design, Screening.

Graphical Abstract

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