Current cardiac safety testing regimes have successfully prevented new drugs coming to market with unknown proarrhythmic risk. However, they are expensive and time-consuming, and an over-reliance on hERG liability as a marker for proarrhythmia has led to exclusion of useful chemical scaffolds from further drug development. In addition, the focus on hERG ignores the risk posed by potential drug interactions with multiple cardiac ion channels (MICE) that can alter cardiac action potentials.
The HESI Cardiac Safety Committee present results from an international ion channel research study that assessed the variability of hERG data generated using automated patch clamp platforms (QPatch 48, Qube 384 and the SyncroPatch 384i) across four different labs.
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).