Automated Tight Seal Electrophysiology for Assessing the Potential hERG Liability of Pharmaceutical Compounds

• DOI: 10.1089/adt.2004.2.497
• Publication Date: 2004-11-17T13:20:16Z
• Authors: Huimin Tao; David Santa Ana; António Guia; Mingxian Huang; Joseph Ligutti; George Walker; Khachonesine Sith...; Florence Chan; Tao Guoliang; Zoya Zozulya; Steve Saya; Rick Phimmachack; Charles Sie; Julian Yuan; Lei Wu; Jia Xu; Andrea Ghetti
• Keywords: hERG; Cardiac Electrophysiology; Torsades de pointes; Potassium channel blocker

Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology most reliable vitro screening method for identifying potential hERG liabilities, but only recent advent planar electrode-based voltage clamp electrophysiology promises sufficient throughput to support drug testing needs discovery programs. We have assessed reliability this new format technology measuring activity small molecules on channel. Based results herein a against panel well-characterized hERG-active and -inactive molecules, we demonstrate that electrode electrophysiology, utilizing Sealchip™ PatchXpress™ platform (AVIVA Biosciences Corp., San Diego, CA), comparable traditional based glass micropipettes its data content. The will allow significantly higher more thorough pharmaceutical compounds.