This protocol details the in vitro hERG channel patch-clamp assay used as an early screen to predict compound-induced QT prolongation in drug development.
Enables early in vitro QT risk screening for new compounds; leaves open standardization and clinical predictive validation.
In vitro electrophysiological safety studies have become an integral part of the drug development process since, in many instances, compound-induced QT prolongation has been associated with a direct block of human ether-a-go-go-related gene (hERG) potassium channels or its native current, the rapidly activating delayed rectifier potassium current (I(Kr)). Therefore, the in vitro hERG channel patch-clamp assay is commonly used as an early screen to predict the ability of a compound to prolong QT interval. The protocol described in this unit is designed to assess the effects of new chemical entities after acute or long-term exposure on the amplitude of I(Kr) in human embryonic kidney 293 (HEK293) cells stably transfected with the hERG channel (whole-cell configuration of the patch-clamp technique). Examples of results obtained with terfenadine, arsenic, pentamidine, erythromycin, and sotalol are provided for illustrative purposes.
No takes yet. Share an insight, caveat, or question.
Goineau et al. (2012) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: