Heat Shock Protein Inhibitors pp 81-129

Part of the Topics in Medicinal Chemistry book series (TMC, volume 19) | Cite as

The Effect of Structure and Mechanism of the Hsp70 Chaperone on the Ability to Identify Chemical Modulators and Therapeutics

  • Alexandra Manos-Turvey
  • Jeffrey L. Brodsky
  • Peter Wipf

Abstract

The role of the Hsp70 molecular chaperone in effecting proper cellular protein folding, transport, and degradation processes, stabilizing protein complexes, and maintaining membrane integrity has long been recognized. More recently, Hsp70 has been linked to severe neurological diseases, such as Alzheimer’s, Parkinson’s and Huntington’s disease, as well as to cystic fibrosis and cancer. As a result, there is a growing interest in the development of small-molecule modulators of Hsp70 function. While several distinct classes of Hsp70 agonists and antagonists have been identified to date, clinical studies with Hsp70-targeted drugs have yet to be initiated, and proof of principle for therapeutic benefits remains to be established. However, a large body of preclinical biological evidence suggests that this chaperone plays a key role in many human diseases associated with protein (un)folding and trafficking and that the continued development of Hsp70 modulators will yield novel therapeutic strategies.

Keywords

15-Deoxyspergualin ADD70 Apoptozole Hsc70 Hsp70 MAL3-101 VER-155008 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Alexandra Manos-Turvey
    • 1
    • 2
  • Jeffrey L. Brodsky
    • 1
  • Peter Wipf
    • 2
  1. 1.Department of Biological SciencesUniversity of PittsburghPittsburghUSA
  2. 2.Department of ChemistryUniversity of PittsburghPittsburghUSA

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