Kelly William K, O'Connor Owen A, Marks Paul A
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Expert Opin Investig Drugs. 2002 Dec;11(12):1695-713. doi: 10.1517/13543784.11.12.1695.
Transformed cells, characterised by inappropriate cell proliferation, do not necessarily lose the capacity to undergo growth arrest under certain stimuli. DNA, genetic information, is packaged in chromatin proteins, for example, histones. The structure of chromatin may be altered by post-translational modifications (e.g., acetylation, phosphorylation, methylation and ubiquitylation) which play a role in regulating gene expression. Two groups of enzymes, histone deacetylases (HDACs) and acetyl transferases, determine the acetylation status of histones. This review focuses on compounds that inhibit HDAC activity. These agents have been shown to be active in vitro and in vivo in causing cancer cell growth arrest, differentiation and/or apoptosis. Several HDAC inhibitors are currently in clinical trials as anticancer agents and, in particular, hydroxamic acid-based HDAC inhibitors have shown activity against cancers at well-tolerated doses.
以不适当的细胞增殖为特征的转化细胞，不一定会丧失在某些刺激下进入生长停滞的能力。DNA（遗传信息）被包装在染色质蛋白中，例如组蛋白。染色质的结构可通过翻译后修饰（如乙酰化、磷酸化、甲基化和泛素化）而改变，这些修饰在调节基因表达中发挥作用。两组酶，即组蛋白脱乙酰酶（HDACs）和乙酰转移酶，决定了组蛋白的乙酰化状态。本综述聚焦于抑制HDAC活性的化合物。这些药物已在体外和体内显示出可使癌细胞生长停滞、分化和/或凋亡的活性。目前有几种HDAC抑制剂正处于抗癌药物的临床试验阶段，特别是基于异羟肟酸的HDAC抑制剂已在耐受良好的剂量下显示出对癌症的活性。
