Action potential response of human induced-pluripotent stem cell derived cardiomyocytes to the 28 CiPA compounds: A non-core site data report of the CiPA study.

We used the whole-cell current clamp technique to examine the response of our in-house hiPSC-CMs to the 28 CiPA-selected compounds, aiming to compare field potential via MEA from core-sites and action potential via current clamp measurement. Our blinded study showed that all seven high-risk test compounds, including bepridil, caused early afterdepolarizations (EADs) at mid-high and/or high concentration(s). All hERG channel blockers in the mid-risk category prolonged APD30 and APD90 at mid-high, and then led to EADs at their respective high concentrations; while chlorpromazine, clarithromycin and risperidone showed little effects. In addition, ranolazine was the only low-risk test compound to prolong APD30 and APD90 at mid-high, and then produce EADs at high concentration. In conclusion, our results generally agreed with data from all core-sites of the CiPA consortium using the MEA method. Moreover, our assay can successfully detect pro-arrhythmic risk of drug candidates such as bepridil with superior sensitivity.