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

大环化合物作为抗癌剂:针对 HDAC、FLT3 和 JAK2 的多作用抑制剂的设计和合成

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作者:Cheng-Qing Ning, Cheng Lu, Liang Hu, Yan-Jing Bi, Lei Yao, Yu-Jun He, Li-Fei Liu, Xiao-Yu Liu, Nie-Fang Yu

Abstract

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.

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