作用于多靶点的组蛋白去乙酰化酶抑制剂结构设计的研究进展

Progress in the Research of Structural Design in Multi-targeted Histone Deacetylase Inhibitors

目的肿瘤产生机制的复杂性,要求对多种促肿瘤发生发展机制同时抑制,才能有效阻止肿瘤生长。组蛋白去乙酰化酶抑制剂(HDACi)作为一种新型抗肿瘤药物,能诱导肿瘤细胞凋亡,阻止癌细胞增长。利用结构的多样性和变通性设计新颖的作用于多靶点的HDACi。方法分类总结大量已被报道的多靶点组蛋白去乙酰化酶抑制剂。结果多靶点抑制剂在临床实验中表现出了较好的抗肿瘤活性。结论多靶点单一分子的HDACi的研究日益引起人们的重视,具有广阔的研发前景。

OBJECTIVE The heterogeneous nature of cancer requires a comprehensive approach for attacking the multiple mechanisms underlying the initiation and progression of cancer. HDACi have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. Design novel multi-target HDACi based on the structural diversity and adaptation. METHODS Classify and summarize large numbers of reported multi-target histone deacetylase inhibitors. RESULTS Multi-target inhibitors in clinical trials show good antitumor activity. CONCLUSION Multi-target single-molecule HDAC inhibitors have attracted much attention, and have broad prosoects for development.