检测钾离子通道的小分子荧光探针的研究进展 - 药学进展.pdf

PROGRESS IN PHARMACEUTICAL SCIENCES 2017,41 1 :41-48 ( ) 41 检测钾离子通道的小分子荧光探针的研究进展 张晓梦，杜吕佩 * （山东大学药学院药物化学研究所 , 山东 济南 250012） [ 摘要 ] 钾离子通道是分布最为广泛、种类繁多的一类离子通道，因其生理功能的多样性，已成为许多疾病的药物作用靶点。近年来，许 多化学结构不同的药物均因钾离子通道阻滞引起的严重心肌毒性而被撤出市场，使得小分子药物的钾通道抑制活性筛选面临重大挑战。 介绍检测钾离子通道的小分子荧光探针的研究进展，并总结小分子荧光探针的作用机制，为今后小分子荧光探针的设计提供思路，使得 小分子荧光探针可以广泛应用于候选药物的高通量筛选、钾离子通道的活体成像与检测。 [ 关键词 ] 钾离子通道；hERG；shaker 钾离子通道；小分子荧光探针 [ 中图分类号 ] R33;R917 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2017）01-0041-08 Research Progress in Small-Molecule Fluorescent Probe for Potassium Channels ZHANG Xiaomeng, DU Lyupei (Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan 250012, China) [Abstract] Potassium channels are the most diverse and widely distributed type of ion channel. Because of their diverse physiological functions, potassium channels have become drug targets for many diseases. In recent years, many drugs with different chemical structures have been withdrawn from the market because of their blockage of potassium channels and subsequent severe cardiac toxicity. As a result, screening of potassium channel inhibitory activities of small-molecule drugs are facing great challenges. This article introduced the research progress in small-molecule fluorescent probes for potassium channels, and summarized their mechanisms, hoping to provide ideas for the future design of small-molecule fluorescent probes and promote their use in high throughput screening of candidate drugs as well as in the in vivo imaging and detecting of potassium ion channels. [Key words] potassium channel; hERG; shaker potassium channel; small molecule fluorescent probe 离子通道是细胞膜上一类非常特殊的亲水性蛋白