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

Author(s):

Daniel T. Gewirth   Pages 2779 - 2791 ( 13 )

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.

Affiliation:

Hauptman-Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY, 14203, USA.

Graphical Abstract:

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