锌依赖的组蛋白去乙酰化酶选择性抑制剂研究进展

组蛋白去乙酰化酶(histone deacetylases,HDACs)抑制剂是当前国际抗肿瘤研究的热点。由于HDAC家族存在多个亚型,而HDAC的各个亚型,特别是锌依赖的HDAC各个亚型(HDAC1-11),其生物学功能及在各种肿瘤中的表达各不相同,导致HDAC泛抑制剂的应用会产生较大的毒副作用,临床应用受到限制。因此特异性强、毒副作用低的,具有亚型选择性的HDAC抑制剂成为抗肿瘤药物研发的趋势。目前已有的亚型选择性HDAC抑制剂主要靶向HDAC1、2、6、8。该文将阐述HDAC抑制剂的发展趋势及现有的HDAC选择性抑制剂的研究进展。

New advances in isoform-selective inhibitors of Zn2+-dependent histone deacetylase

Histone deacetylases ( HDACs) have emerged as attractive drug targets. This large family consists of 18 enzymes. These isoforms have generally distinct gene expression patterns and are also different in cellular localization and function. Therefore the pan-inhibitors exhibited toxicities in the clinic that might limit their potential,particularly in solid tumors. It may be possible to reduce the toxicity by selectively targeting only the specific isoform( s) involved in maintaining one particular tumor and not affecting other isoforms that are uninvolved or even beneficial. And this opinion has become a more promising strategy. The current existing HDAC selective-inhibitors mainly target HDAC 1, 2,6,8. In this review the developing trend of HDAC inhibitor and the studies about HDAC selective-inhibitors are presented.