Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Int J Mol Sci. 2019 Apr 1;20(7):1616. doi: 10.3390/ijms20071616.
Histone deacetylase inhibitors (HDIs) are a class of prominent epigenetic drugs that are currently being tested in hundreds of clinical trials against a variety of diseases. A few compounds have already been approved for treating lymphoma or myeloma. HDIs bind to the zinc-containing catalytic domain of the histone deacetylase (HDACs) and they repress the deacetylase enzymatic activity. The broad therapeutic effect of HDIs with seemingly low toxicity is somewhat puzzling when considering that most HDIs lack strict specificity toward any individual HDAC and, even if they do, each individual HDAC has diverse functions under different physiology scenarios. Here, we review recent mechanistic studies using omics approaches, including epigenomics, transcriptomics, proteomics, metabolomics, and chemoproteomics, methods. These omics studies provide non-biased insights into the mechanism of action for HDIs.
组蛋白去乙酰化酶抑制剂（HDACIs）是一类重要的表观遗传药物，目前正在针对多种疾病进行数百项临床试验。已有几种化合物被批准用于治疗淋巴瘤或骨髓瘤。HDACIs 与含锌的组蛋白去乙酰化酶（HDACs）的催化结构域结合，并抑制去乙酰化酶的酶活性。当考虑到大多数 HDACIs 对任何单个 HDAC 缺乏严格的特异性，即使它们确实如此，每个单独的 HDAC 在不同的生理情况下也具有不同的功能时，HDACIs 具有广泛的治疗效果和似乎较低的毒性就有些令人费解。在这里，我们回顾了使用组学方法（包括表观基因组学、转录组学、蛋白质组学、代谢组学和化学蛋白质组学）的最新机制研究。这些组学研究为 HDACIs 的作用机制提供了无偏见的见解。
