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Indexed by:Journal Papers

First Author:Xiao, Yan

Correspondence Author:Liu, YJ (reprint author), Dalian Univ Technol, Sch Life Sci & Med, Dagong Rd 2, Panjin 124221, Peoples R China.

Co-author:Liu, Yajun

Date of Publication:2020-01-01

Journal:CURRENT DRUG TARGETS

Included Journals:SCIE、PubMed

Volume:21

Issue:3

Page Number:302-317

ISSN No.:1389-4501

Key Words:HSP90; anticancer; drug design; HSP90 inhibitor; HSP90 beta; GRP94; lead optimization

Abstract:HSP90 is a member of the family of heat shock proteins responsible for folding proteins into mature conformations and thus maintaining their biological function in cells. Since it is involved in all hallmarks of cancer, HSP90 has been considered as a promising drug target for cancer therapy. Eighteen HSP90 inhibitors have entered clinical trials, however, none has been approved by the FDA. There is still a great need for novel HSP90 inhibitors with strong anticancer activity and good safety profile. In the past several years, many new molecules were identified as HSP90 inhibitors and some of them have shown promising pharmacological profiles in preclinical evaluations. In this review, HSP90 inhibitors identified from 2014 to date are summarized and their design strategies, chemical structures, and biological activities are reviewed. The inhibitors are categorized by their different target domains and selectivity as N-terminal, C-terminal, and isoform-selective HSP90 inhibitors.