Profiling technologies for the identification and characterization of small-molecule histone deacetylase inhibitors.
Profiling technologies for the identification and characterization of small-molecule histone deacetylase inhibitors.
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DOI：
10.1016/j.ddtec.2015.10.006
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Liao D
中科院分区：
文献类型：
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作者：
Liao D
组蛋白脱乙酰酶 (HDAC) 是治疗癌症、神经系统、炎症和代谢疾病的有希望的药物靶点。四种 HDAC 小分子抑制剂已获得监管部门批准用于治疗淋巴瘤和多发性骨髓瘤。高度灵敏的体外和基于细胞的分析技术已被开发用于发现 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个残基分辨率下定义抑制剂的特异性。化学蛋白质组学分析可以确定抑制剂对细胞提取物中特定 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改善 HDAC 亚型特异性和药物特性特别感兴趣，因此有效的分析技术将继续具有重要的用途。在这里，我们简要回顾 HDAC 抑制剂分析技术的最新发展，并讨论各种技术的独特特征。
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.