新型和新兴的 HDAC 抑制剂在癌症治疗中的应用。
New and emerging HDAC inhibitors for cancer treatment.
出版信息
J Clin Invest. 2014 Jan;124(1):30-9. doi: 10.1172/JCI69738. Epub 2014 Jan 2.
Abstract
Epigenetic enzymes are often dysregulated in human tumors through mutation, altered expression, or inappropriate recruitment to certain loci. The identification of these enzymes and their partner proteins has driven the rapid development of small-molecule inhibitors that target the cancer epigenome. Herein, we discuss the influence of aberrantly regulated histone deacetylases (HDACs) in tumorigenesis. We examine HDAC inhibitors (HDACis) targeting class I, II, and IV HDACs that are currently under development for use as anticancer agents following the FDA approval of two HDACis, vorinostat and romidepsin.
摘要
表观遗传酶在人类肿瘤中经常通过突变、表达改变或不适当的募集到特定基因座而失调。这些酶及其伴侣蛋白的鉴定推动了针对癌症表观基因组的小分子抑制剂的快速发展。本文讨论了异常调节的组蛋白去乙酰化酶 (HDACs) 在肿瘤发生中的影响。我们研究了目前正在开发的针对 I 类、II 类和 IV 类 HDAC 的 HDAC 抑制剂 (HDACis)，在 FDA 批准了两种 HDACis（伏立诺他和罗米地辛）后，这些抑制剂被用作抗癌药物。
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