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Updated: Aug 13, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Identification of a pharmacophore of SKCa channel blockers
Sebastien Dilly1, Amaury Graulich, Amaury Farce
1Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, EA1 043, 3 rue du professeur Laguesse, BP 83, 59006 Lille Cedex, France.
Abstract:
Small conductance calcium-activated potassium channels (SK) are widely expressed throughout the central nervous system (CNS) and the periphery. Three subtypes of SK channels have so far been identified in different parts of the brain. Activation of the SK channels by a rise in intracellular calcium leads to the hyperpolarisation of the membrane, reducing cell excitability. Blocking the SK channels might be beneficial in the treatment of depression, Parkinson's disease and cognitive disorders. However, few blockers of SK channels have been characterized. In this study, a pharmacophoric model of SK channels blockers is presented. It is based on a series of nonpeptidic compounds and apamin, a peptidic blocker. To create the pharmacophore model, the conformational space of nonpeptidic blockers was investigated to generate a series of distance constraints applied to a simulated annealing study of apamin. The resulting conformation was superimposed with the nonpeptidic blockers to give a pharmacophore.
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