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

Curr Top Med Chem. 2016;16(25):2779-91. doi: 10.2174/1568026616666160413141154.


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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / chemistry
  • Humans
  • Resorcinols / chemistry
  • Sequence Homology, Amino Acid


  • HSP90 Heat-Shock Proteins
  • Resorcinols
  • resorcinol