Trend of histone deacetylase inhibitors in cancer therapy: isoform selectivity or multitargeted strategy.
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.
Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, Shandong, China.
Lei
L
Zhang
Yantao
Y
Han
Qixiao
Q
Jiang
Chunbo
C
Wang
Xuehong
X
Chen
Xiaoguang
X
Li
Fuming
F
Xu
Yuqi
Y
Jiang
Qiang
Q
Wang
Wenfang
W
Xu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D020033:Protein Isoforms / Q000187:drug effects*
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D020033:Protein Isoforms
bifunctional molecule; histone deacetylase; inhibitors; multitargeted; selectivity