Optimization of hERG screening using IonFlux HT automated system

Eric GUILLEMARE, Jean-Philippe BERTRAND, Patrick VERGÈS, Priscilla BRUN and Jean-Pierre MARTINOLLE
Sanofi Research & Development
Platform Disposition, Safety and Animal Research (DSAR), Preclinical Safety, Safety Pharmacology Montpellier, France
 

Abstract:

The human Ether-à-go-go related gene (hERG) represents the molecular correlate of the IKr current, one of the several potassium currents involved in cardiac action potential repolarization. It is widely accepted that for most compounds, the primary mechanism for QT interval prolongation is direct inhibition of the IKr current. Therefore, compound testing for hERG inhibition is critical in the early safety evaluation process. To access directly to effects of compounds on channel function, only electrophysiological technique is required. The most classical technique is the conventional patch-clamp but the output is limited. Planar automated path-clamp systems have been developed to increase this output including IonWorks, Qpatch and Patchxpress. Because the introduction of planar system was drastically increased the cost of hERG test, the development of the new technology drives a tradeoff between data quality and cost of production. Here we describe the ability of IonFlux HT® automated patch-clamp system (Fluxion Biosciences) to study hERG current inhibition versus an other automated patch-clamp system (patchXpress) and conventional patch-clamp. 

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