A critical component of the CiPA initiative’s modernized cardiac safety framework is the use of computational models to predict arrhythmic risk — models that depend on accurate measurements of how drugs interact with the hERG ion channel. To address this, the Ion Channel Working Group developed and standardized a patch-clamp protocol capable of measuring both the potency and kinetics of hERG channel block, with an eye toward broad implementation on automated platforms across the industry. Testing a panel of twelve reference drugs, the group successfully characterized block potency, time course, and trapping behavior for the majority of compounds — though seven drugs exhibited binding kinetics too rapid to be reliably captured by a single protocol, highlighting an inherent challenge in developing a one-size-fits-all approach. The resulting dataset is now being used by CiPA’s In Silico Working Group to build drug-binding models for risk prediction and has been made freely available as a gold-standard reference for evaluating variability across high-throughput testing platforms.

PUBLICATION: Journal of Pharmacological and Toxicological Methods (2017)

AUTHORS: Monique Windley, Najah Abi-Gerges, Bernard Fermini, Jules Hancox, et al.