Aparicio Ana
Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
Clin Lung Cancer. 2006 Mar;7(5):309-12. doi: 10.3816/CLC.2006.n.011.
In the nucleus, DNA is wrapped around octamers of histone proteins. Histones, like other proteins, are posttranslationally modified by the addition of an array of chemical groups that affect their interactions with surrounding structures. Histone acetyltransferases and histone deacetylases (HDACs) are the enzymes involved in the addition and removal, respectively, of acetyl groups from the aminoterminal tails of histones. A number of structurally diverse compounds are capable of inhibiting HDACs and exert a variety of biologic effects on cancer cells in preclinical models. Early clinical trials with the first generation of HDAC inhibitors (HDACIs) have demonstrated promising therapeutic activity, and HDACs have become one of the hottest targets in drug development today.
在细胞核中，DNA缠绕在组蛋白八聚体周围。组蛋白与其他蛋白质一样，在翻译后会通过添加一系列化学基团进行修饰，这些化学基团会影响它们与周围结构的相互作用。组蛋白乙酰转移酶和组蛋白去乙酰化酶（HDACs）分别是参与从组蛋白氨基末端尾巴添加和去除乙酰基的酶。许多结构多样的化合物能够抑制HDACs，并在临床前模型中对癌细胞发挥多种生物学效应。第一代HDAC抑制剂（HDACIs）的早期临床试验已显示出有前景的治疗活性，HDACs已成为当今药物开发中最热门的靶点之一。
