Cloxyquin (5-chloroquinolin-8-ol) is an activator of the two-pore domain potassium channel TRESK
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- 作者：Paul D. Wright ; Gregory Weir ; Jamie Cartl ; David Tickle ; Catherine Kettleborough ; M. Zameel Cader ; Jeff Jerman
- 关键词：TRESK ; Migraine ; Screening ; Assay ; Ion channel ; Cloxyquin
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：15 November, 2013
- 年：2013
- 卷：441
- 期：2
- 页码：463-468
- 全文大小：1080 K
文摘
TRESK is a two-pore domain potassium channel. Loss of function mutations have been linked to typical migraine with aura and due to TRESK鈥檚 expression pattern and role in neuronal excitability it represents a promising therapeutic target. We developed a cell based assay using baculovirus transduced U20S cells to screen for activators of TRESK. Using a thallium flux system to measure TRESK channel activity we identified Cloxyquin as a novel activator. Cloxyquin was shown to have an EC50 of 3.8 渭M in the thallium assay and displayed good selectivity against other potassium channels tested. Activity was confirmed using whole cell patch electrophysiology, with Cloxyquin causing a near two fold increase in outward current. The strategy presented here will be used to screen larger compound libraries with the aim of identifying novel chemical series which may be developed into new migraine prophylactics.