CHAPTER 11: Hsp70 Inhibitors
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Published:23 Oct 2013
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Series: Drug Discovery
Y. Chen and W. Zhou, in Inhibitors of Molecular Chaperones as Therapeutic Agents, ed. T. D. Machajewski and Z. Gao, The Royal Society of Chemistry, 2013, pp. 302-317.
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Hsp70 proteins function as ATP-dependent molecular chaperones, which are involved in the folding of newly synthesized polypeptides, the assembly of multi-protein complexes and the transport of proteins across cellular membranes. Hsp70 is crucial for maintaining protein homeostasis, thus disregulation of Hsp70 is found in many human diseases, such as cancer and Parkinson*s disease, where Hsp70 is thought to be a potential target. To target Hsp70, several compounds were identified to inhibit the functions of Hsp70 through different mechanisms. In this chapter, we introduce the major chemical platforms for screening Hsp70 inhibitors and describe ten different Hsp70 inhibitors including structural features, the binding mechanisms and cellular functions. Lastly, we discuss the prospects for the development of Hsp70 inhibitors.