Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2

作者:Ning, Cheng-Qing; Lu, Cheng; Hu, Liang; Bi, Yan-Jing; Yao, Lei; He, Yu-Jun; Liu, Li-Fei; Liu, Xiao-Yu; Yu, Nie-Fang*
来源:European Journal of Medicinal Chemistry, 2015, 95: 104-115.
DOI:10.1016/j.ejmech.2015.03.034

摘要

A novel series of macrocyclic compounds were designed and synthesized as multi-target inhibitors targeting HDAC, FLT3 and JAK2. Some of these compounds exhibited potent HDAC inhibition as well as FLT3 and JAK2 inhibition under both cell-free and cellular conditions. In vitro antiproliferative assay indicated that these compounds were interestingly more cytotoxic to MV4-11 cells bearing FLT3-ITD mutation and HEL cells bearing JAK2(V617F) mutation.