School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
J Med Chem. 2020 Nov 12;63(21):12460-12484. doi: 10.1021/acs.jmedchem.0c00830. Epub 2020 Jul 16.
It is now 30 years since the first report of a potent zinc-dependent histone deacetylase (HDAC) inhibitor appeared. Since then, five HDAC inhibitors have received regulatory approval for cancer chemotherapy while many others are in clinical development for oncology as well as other therapeutic indications. This Perspective reviews the biological and medicinal chemistry advances over the past 3 decades with an emphasis on the design of selective inhibitors that discriminate between the 11 human HDAC isoforms.
自第一篇强效锌依赖组蛋白去乙酰化酶 (HDAC) 抑制剂的报道出现以来，已经过去了 30 年。此后，有 5 种 HDAC 抑制剂获得了癌症化疗的监管批准，而许多其他抑制剂则正在临床开发中，用于肿瘤学以及其他治疗适应症。本文从生物学和药物化学的角度，重点介绍选择性抑制剂在区分 11 种人类 HDAC 同工酶方面的设计，回顾过去 30 年的进展。
