环肽类组蛋白去乙酰化酶抑制剂

组蛋白乙酰化转移酶(HAT)和组蛋白去乙酰化酶(HDAC)调节组蛋白乙酰化程度，HDAC在基因表达和染色体形成等方面起着重要的调节作用。HDAC抑制剂能够引起肿瘤细胞生长停滞、诱导肿瘤细胞分化和调亡。通过对各种HDAC抑制剂结构及作用机制的研究有助于该类药物在临床上的应用和拓宽癌症治疗的适用范围。本文概述了近年来天然及合成的环肽类组蛋白去乙酰化酶抑制剂的研究进展。

Cyclic Peptide Histone Deacetylases Inhibitors

Histone acetyltransferases(HAT) and histone deacetylases(HDACs) as the corresponding enzymes regulate the change of histones in two antagonist forms,acetylated or deacetylated.In recent years,inhibition of HDACs has emerged as a potential strategy in human cancer therapy,since these enzymes play a fundamental role in regulating gene expression and chromatin assembly.The histone deacetylases inhibitors(HDACIs) are potent inducers of growth arrest,differentiation and apoptosis of tumor cells,and have entered clinical trials for both solid and liquid tumors.However,the molecular basis for their anticancer selectivity remains largely unknown.An improved understanding of the structure and action mechanism of HDAC inhibitors will likely accelerate the clinical development and broaden the future scope and utility of HDAC inhibitors for cancer treatment.In this review, we summarize recent advances of the HDACs inhibitors of cyclic peptide in structure,mechanism of action,clinical development.