Molecular structure of hERG

hERG Channel Electrophysiology Overview

Drug-induced delayed cardiac repolarization has associated with block of hERG (a functionally prominent ventricular repolarizing potassium current) and is linked to cardiac proarrhythmia (Torsades-de-Pointes). However, hERG current block is not always associated with delayed repolarization, and preclinical cardiac safety studies evaluating only hERG current provide a focused but narrow perspective. Additional cardiac ion channels represent numerous potential off-target effects that may modulate the effects of hERG current block, affect impulse initiation (chronotropic effects), conduction (dromotropic effects), or contractility (inotropic effects). Routine hERG screening in early discovery efforts should be supplemented with additional studies to avoid unduly discarding hERG blocking drugs not affecting delayed repolarization and to ensure overall cardiac safety.

Assessing hERG Channel Inhibition

  • BioMaxLab uses manual patch clamp (a gold standard) to assess hERG channel inhibition on HEK293 cells or CHO cells stably transfected with the hERG ion channel.
  • BioMaxLab uses manual patch clamp (a gold standard) to assess hERG channel inhibition on HEK293 cells or CHO cells stably transfected with the hERG ion channel.
  • Protocols include exploratory non-GLP screening of single high concentration or IC50.
  • Validated with a number of agents known to affect the hERG current, including terfenadine, cisapride and E-4031.

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