Liao Daiqing
Department of Anatomy and Cell Biology, University of Florida College of Medicine, UF Health Cancer Center, UF Genetics Institute, Gainesville, FL 32610-0235, United States.
Drug Discov Today Technol. 2015 Nov;18:24-8. doi: 10.1016/j.ddtec.2015.10.006. Epub 2015 Nov 3.
Histone deacetylases (HDACs) are promising drug targets for treating cancer, neurologic, inflammatory and metabolic diseases. Four small molecule inhibitors of HDACs have gained regulatory approval for treating lymphomas and multiple myelomas. Highly sensitive in vitro and cell-based profiling technologies have been developed to discover HDAC inhibitors (HDACi) and characterize their inhibitory potency, target-binding specificity and kinetics. In particular, proteomic profiling can define the specificity of an inhibitor at a single residue resolution. Chemoproteomic profiling can determine the potency, specificity and binding kinetics of an inhibitor on a specific HDAC complex in cell extracts. As inhibitors with new chemical scaffolds are of particular interest to improve HDAC isoform-specificity and pharmaceutical properties, effective profiling technologies will continue to have important utility. Here we briefly review recent developments of HDAC inhibitor profiling technologies and discuss distinct features of various technologies.
组蛋白去乙酰化酶（HDACs）是治疗癌症、神经疾病、炎症和代谢疾病的有前景的药物靶点。四种HDAC小分子抑制剂已获得监管批准用于治疗淋巴瘤和多发性骨髓瘤。已经开发出高度灵敏的体外和基于细胞的分析技术来发现HDAC抑制剂（HDACi）并表征其抑制效力、靶点结合特异性和动力学。特别是，蛋白质组分析可以在单残基分辨率下定义抑制剂的特异性。化学蛋白质组分析可以确定抑制剂在细胞提取物中对特定HDAC复合物的效力、特异性和结合动力学。由于具有新化学支架的抑制剂对于提高HDAC亚型特异性和药物性质特别有意义，有效的分析技术将继续具有重要用途。在此，我们简要回顾HDAC抑制剂分析技术的最新进展并讨论各种技术的独特特征。
