药物代谢酶特异性探针底物的研发与应用进展.pdfVIP

PROGRESS IN PHARMACEUTICAL SCIENCES 2017,41 2 :110-123 110 ( ) 药物代谢酶特异性探针底物的研发与应用进展 王丹丹 ，宁静 ，吕侠 ，葛广波1 2 2 1,2* （1. 上海中医药大学系统药代动力学中心，上海 201203；2. 中国科学院大连化学物理研究所，辽宁 大连 116023） [ 摘要 ] 人体内分布数百种结构多样、功能各异的药物代谢酶，其表达和功能易受遗传和环境因素的影响，导致其在不同人种、个体及组织 中的分布都不尽相同。特异性探针底物作为药物代谢酶活性表征的关键工具分子，其在新药发现、药-药相互作用评价、临床药理学及精准 医学检测等领域具有重要的应用价值。围绕人体分布的重要药物代谢酶，综述其特异性探针底物的设计研发及生物医学应用进展，以期为 药物代谢酶的精准检测及相关应用研究提供参考。 [ 关键词 ] 药物代谢酶；特异性探针底物；酶抑制剂；药-药相互作用；生物医学应用 [ 中图分类号 ] R969.1 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2017）02-0110-14 Research Progress in Specific Probe Substrates for Drug Metabolizing Enzymes 1 2 2 1,2 WANG Dandan , NING Jing , LYU Xia , GE Guangbo (1. Center for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; 2. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China) [Abstract] There are hundreds of drug metabolizing enzymes (DMEs) found in human body. The expression and function of DMEs are easily affected by genetic and environmental factors, leading to variations in distribution across different human species, individuals and tissues. As the key tools for characterization of enzymatic activities of DMEs, highly specific probe substrates are widely used in drug discovery, evaluation of drug-drug interactions (DDIs), clinical pharmacology and precision medicine. This review summarized the research progress in the development and biomedical applications of specific probe substrates for major DMEs, so as to provide reference for precise determination of DMEs and related applications. [Key words] drug metabolizing enzyme; specific probe substrate; enzyme inhibitor; drug-drug interaction