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Updated: Aug 29, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Structure-based discovery of potassium channel blockers from natural products: virtual screening and
Hong Liu1, Yang Li, Mingke Song
1Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 201203, Shanghai, People's Republic of China.
Abstract:
Potassium ion (K(+)) channels are attractive targets for rational drug design. Based upon a three-dimensional model of the eukaryotic K(+) channels, the docking virtual screening approach was employed to search the China Natural Products Database. Compounds were ranked according to the relative binding energy, favorable shape complementarity, and potential of forming hydrogen bonds with the K(+) channel. Four candidate compounds found by virtual screening were investigated by using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. When applied extracellularly, compound 1 markedly depressed the delayed rectifier K(+) current (I(K)) and fast transient K(+) current (I(A)), whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory effect on I(K). Intracellular application of the four compounds had no effect on both the K(+) currents.
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