Novel cell-free high-throughput screening method for pharmacological tools targeting K+ channels

作者：Su Zhenwei; Brown Emily C; Wang Weiwei; MacKinnon Roderick^*

来源：Proceedings of the National Academy of Sciences, 2016, 113(20): 5748-5753.

DOI：10.1073/pnas.1602815113

• liposome flux assay
• LFA
• K+ channel screening
• hERG safety assay

K+ channels, a superfamily of similar to 80 members, control cell excitability, ion homeostasis, and many forms of cell signaling. Their malfunctions cause numerous diseases including neuronal disorders, cardiac arrhythmia, diabetes, and asthma. Here we present a novel liposome flux assay (LFA) that is applicable to most K+ channels. It is robust, low cost, and high throughput. Using LFA, we performed small molecule screens on three different K+ channels and identified new activators and inhibitors for biological research on channel function and for medicinal development. We further engineered a hERG (human ether-a-go-go-related gene) channel, which, when used in LFA, provides a highly sensitive (zero false negatives on 50 hERG-sensitive drugs) and highly specific (zero false positives on 50 hERG-insensitive drugs), low-cost hERG safety assay.

• 出版日期2016-5-17