Journal
MEDICINAL RESEARCH REVIEWS
Volume 35, Issue 1, Pages 63-84Publisher
WILEY
DOI: 10.1002/med.21320
Keywords
histone deacetylase; inhibitors; selectivity; multitargeted; bifunctional molecule
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Funding
- Chinese National Science Fund [21102185, 81173593]
- Shandong Science Fund [ZR2011HM046]
- Qingdao Technology Fund [12-1-3-39-nsh]
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Pharmacological inhibition of histone deacetylases (HDACs) has been successfully applied in the treatment of a wide range of disorders, including Parkinson's disease, infection, cardiac diseases, inflammation, and especially cancer. HDAC inhibitors (HDACIs) have been proved to be effective antitumor agents by various stages of investigation. At present, there are two opposite focuses of HDACI design in the cancer therapy, highly selective inhibitor strategy and dual- or multitargeted inhibitors. The former method, which is supposed to elucidate the function of individual HDAC and provide candidate inhibitors with fewer side effects, has been widely accepted by the inhibitor developer. The latter approach, though less practiced, has promising potential for the antitumor therapy based on HDACIs. Effective HDACIs, some of which are in clinic anticancer research, have been developed by both methods. In order to gain insight into HDACI design, the strategies and achievements of the two diverse methods are reviewed.
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