Zwergel Clemens, Valente Sergio, Jacob Claus, Mai Antonello
Sapienza University of Rome, Department of Drug Chemistry and Technologies , Piazzale Aldo Moro 5, 00185 Rome , Italy +00390649913392 ;
Expert Opin Drug Discov. 2015 Jun;10(6):599-613. doi: 10.1517/17460441.2015.1038236. Epub 2015 Apr 20.
Histone deacetylases (HDACs) are key players in the mediation of gene expression for both cancerous and noncancerous malignancies. Overexpression of these enzymes has been demonstrated in numerous types of cancer with some enzyme isoforms also involved in neurological, inflammatory and viral pathologies. Hence, the development of HDAC inhibitors (HDACis) represents a promising approach for their treatment. Numerous chemical entities have been studied in the recent years and some of them have reached clinical trials.
This review summarizes the recent efforts in the drug development of HDACis and their potential application as therapeutic agents in cancerous, neurological, inflammatory and viral diseases.
The development of novel potent and selective HDACis is ongoing. However, increased scientific effort is needed to aid the fight of specific types of cancerous or noncancerous disease with more selective agents required to avoid side effects during therapy. An interesting therapeutic approach is the use of HDACis in combination with other epigenetic target modulators to combine their therapeutic potential for a synergistic effect.
组蛋白去乙酰化酶（HDACs）是介导癌症和非癌症恶性肿瘤基因表达的关键因子。这些酶在多种类型的癌症中均有过表达，一些酶亚型还与神经、炎症和病毒病理学有关。因此，开发HDAC抑制剂（HDACis）是一种很有前景的治疗方法。近年来，人们对众多化学实体进行了研究，其中一些已进入临床试验阶段。
本综述总结了近年来HDACis药物研发的成果及其作为治疗剂在癌症、神经、炎症和病毒疾病中的潜在应用。
新型强效和选择性HDACis的研发正在进行中。然而，需要加大科研力度，以帮助对抗特定类型的癌症或非癌症疾病，需要更具选择性的药物来避免治疗期间的副作用。一种有趣的治疗方法是将HDACis与其他表观遗传靶点调节剂联合使用，以结合它们的治疗潜力产生协同效应。
