1. Academic Validation
  2. Novel cell-free high-throughput screening method for pharmacological tools targeting K+ channels

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

  • Proc Natl Acad Sci U S A. 2016 May 17;113(20):5748-53. doi: 10.1073/pnas.1602815113.
Zhenwei Su 1 Emily C Brown 1 Weiwei Wang 1 Roderick MacKinnon 2
Affiliations

Affiliations

  • 1 Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
  • 2 Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 mackinn@rockefeller.edu.
Abstract

K(+) channels, a superfamily of ∼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-à-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.

Keywords

K+ channel screening; LFA; hERG safety assay; liposome flux assay.

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