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Paralog Specific Hsp90 Inhibitors - A Brief History and a Bright Future.

ABSTRACT: BACKGROUND:The high sequence and structural homology among the hsp90 paralogs - Hsp90?, Hsp90?, 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.

SUBMITTER: Gewirth DT

PROVIDER: S-EPMC4995118 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Paralog Specific Hsp90 Inhibitors - A Brief History and a Bright Future.

Gewirth Daniel T DT

Current topics in medicinal chemistry 20160101 25

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Results</h4>First generation compounds that selectively bind to Hsp90, Grp94, or Trap-1 have been identified ...[more]

PMID: 27072700

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