Predicting cardiac proarrhythmic risk exclusively using automated patch-clamp data

Poster Description

Recent work by FDA and HESI CiPA working groups indicate that in vitro hERG, Nav1.5 and Cav1.2 potency data in addition to dynamic hERG kinetic data is required to accurately predict proarrhythmic risk. Below we explore two key challenges in exclusively using automated patch-clamp for risk prediction:

  1. Metrion has previously shown the ability to implement the difficult Milnes protocol on QPatch, but the challenges of producing full concentration response formats required for in silico models are unknown.
  2. Estimating accurate potencies for Cav1.2 inhibitors such as verapamil that match manual patch-clamp values and allow prediction of Multiple Ion Channel Effect (MICE) profiles with reduced proarrhythmia risk.
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Recommended Publications
Latest Publications
Assessing the Variability of hERG Data Generated Using a Mock Action Potential Waveform and Automated Patch Clamp Platforms

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.

Using high-throughput automated patch clamp electrophysiology to identify novel TREK-1 modulators in an animal venom library

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).

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