Moradei Oscar, Vaisburg Arkadii, Martell Robert E
MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montreal, QC, H4S 2A1, Canada.
Curr Top Med Chem. 2008;8(10):841-58. doi: 10.2174/156802608784911581.
Histone deacetylase (HDAC) inhibitors constitute a novel and growing class of anticancer agents that function by altering intracellular patterns of histone acetylation, the so-called epigenetic "histone code," thereby producing changes in cell cycle arrest, differentiation, and/or apoptosis in tumor cells. This overview describes the chemistry and preliminary characterization of recently disclosed molecules in three major classes of HDAC inhibitors: hydroxamic acids, 2-amino- benzanilides, and cyclic peptides. In addition, results from recent clinical trials on isotype-selective HDAC inhibitors are reviewed. It is clear from the plethora of new molecules and the encouraging results from clinical trials that HDAC inhibitors hold a great deal of promise, particularly as add-on therapy, for the treatment of a variety of solid and hematologic cancers.
组蛋白去乙酰化酶（HDAC）抑制剂是一类新型且不断发展的抗癌药物，其作用机制是改变细胞内组蛋白乙酰化模式，即所谓的表观遗传“组蛋白密码”，从而使肿瘤细胞出现细胞周期停滞、分化和/或凋亡等变化。本综述描述了HDAC抑制剂三大主要类别中最近披露的分子的化学结构和初步特性：异羟肟酸类、2-氨基苯甲酰胺类和环肽类。此外，还综述了近期关于亚型选择性HDAC抑制剂的临床试验结果。从大量新分子以及临床试验令人鼓舞的结果可以明显看出，HDAC抑制剂在治疗多种实体癌和血液系统癌症方面具有很大的前景，尤其是作为辅助治疗。
