基于离子通道的药物筛选技术.pdf

ION CHANNELS Screening Technologies for Ion Channel Targets in Drug Discovery Wei Zheng, Ph.D.1 and Laszlo Kiss, Ph.D.2 Merck Research Laboratories 1Department of Automated Biotechnology and 2 Department of Molecular Pharmacology, Pennsylvania Key words: ion channels, HTS, screening assays, screening tech- changes in membrane potential. Ligand-gated channels transition in nologies, ion channel safety. between these states in response to the binding and unbinding of a lig- and. In the open state, ions can flow through a single ion channel pore on channels are important targets for therapeutic intervention. at prodigious rates of over 107 ions per second. Cell-based functional Increasing demand in screening throughput as well as the quality assays are an essential requirement for the screening of ion channels Iof ion channel screening assays has greatly driven innovation of at both the primary and secondary levels. Traditional methods devel- assay technologies and screening instrumentation for ion channel tar- oped for high throughput screening of ion channels, such as binding, gets in last 5 to 10 years. This review article will evaluate currently ion flux and fluorescent probes, measure ion channel activity indi- available screening technologies for ion channels including binding rectly. Patch clamp electrophysiology is regarded as the gold stan- assays, ion flux assays, fluorescence-based assays, and automated dard for measuring ion channel activity and pharmacology. Patch- patch-clamp instrumentation. clamp allows