CiPA update: Refining in vitro cardiac ion channel assays, in silico models and iPSC cardiomyocyte reagents for improved proarrhythmia risk prediction

Poster Description

Metrion is working towards the requirements of the FDA’s Comprehensive in vitro Proarrhythmia (CiPA) initiative (cipaproject.org) which comprises 3 parts: 1) High quality in vitro cardiac ion channel assays, 2) Comprehensive in silico action potential (AP) models, and 3) Predictive assays using induced pluripotent stem cell derived cardiomyocytes (iPSC-CM).

We are building upon our panel of in vitro human cardiac ion channel assays and applying the data to various in silico cardiac models, and more recently assessing commercially available iPSC-CM for use in phenotypic assays to assess the pharmacological and risk predictions from our in vitro and in silico cardiac safety data.

Here we outline our progress in validating and implementing all 3 pillars of the CiPA regime by building upon work presented previously at the 2015 SPS meeting in Prague.

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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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Metrion Biosciences is a contract research organisation (CRO) specialising in high-quality preclinical drug discovery services.
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