Gill Sikander, Gill Raj, Lee Soo Sen, Hesketh J Christian, Fedida David, Rezazadeh Saman, Stankovich Larisa, Liang Dong
Aurora Biomed Inc, Vancouver, BC, Canada.
Assay Drug Dev Technol. 2003 Oct;1(5):709-17. doi: 10.1089/154065803770381066.
Ion channels have been identified as therapeutic targets in various disorders, such as cardiovascular disease, neurological disease, and cystic fibrosis. Flux assays to detect functional ionic flux through ion channels are becoming increasingly popular as tools for screening compounds. In an optimized flux assay, modulation of ion channel activity may produce readily detectable changes in radiolabeled or nonradiolabeled ionic flux. Technologies based on flux assays are currently available in a fully automated high throughput format for efficient screening. This application offers sensitive, precise, and reproducible measurements giving accurate drug rank orders matching those of patch clamp data. Conveniently, the flux assay is amenable to adaptation for different ion channels, such as potassium, sodium, calcium, and chloride channels, by using suitable tracer ions. The nonradiolabeled rubidium-based flux assay coupled with the ion channel reader (ICR) technology has become very successful in ion channel activity analysis and is emerging as a popular technique in modern drug discovery.
离子通道已被确定为多种疾病的治疗靶点，如心血管疾病、神经疾病和囊性纤维化。作为筛选化合物的工具，检测通过离子通道的功能性离子通量的通量测定法越来越受欢迎。在优化的通量测定中，离子通道活性的调节可能会在放射性标记或非放射性标记的离子通量中产生易于检测的变化。基于通量测定的技术目前以全自动高通量形式提供，用于高效筛选。该应用提供灵敏、精确和可重复的测量，给出与膜片钳数据相匹配的准确药物排名顺序。方便的是，通过使用合适的示踪离子，通量测定适用于不同的离子通道，如钾通道、钠通道、钙通道和氯通道。基于非放射性铷的通量测定与离子通道读数器（ICR）技术相结合，在离子通道活性分析中非常成功，并正在成为现代药物发现中的一种流行技术。
