The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is a new cardiac safety testing proposal sponsored by the FDA to refine the current ICH S7B and E14 guidelines. Two components of CiPA utilise in vitro electrophysiological assays that require validation using a toolbox of compounds with defined clinical proarrhythmic risk. Here we outline our progress to optimise these electrophysiological assays to meet the CiPA goal of predicting human cardiac liability.
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).
Scientifica’s PatchScope Pro is an integrated electrophysiology rig incorporating an inverted phase-contrast fluorescence microscope, motorised XY stage and PatchStar micromanipulators, suitable for patch-clamp recording.