Assessing the Variability of hERG Data Generated Using a Mock Action Potential Waveform and Automated Patch Clamp Platforms - A HESI-Coordinated, Multi-Laboratory Comparison of 28 Drugs Across 3 Platforms

Poster Description

At the Safety Pharmacology Society 2024 meeting, a Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee poster presented 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. The experimental methods were standardized as much as possible, which included the use of a mock action potential voltage protocol.

The assay was used to assess the potency of twenty-eight compounds, with known proarrhythmic liability profiles, on the hERG potassium channel. While no systematic differences in the results were observed amongst the participating labs, the overall variability was estimated as 16x using random-effect meta-analysis accounting for drug- and lab-specific effects whixch is higher than that obtained using the conventional manual patch-clamp technique. Concentration verification analysis revealed that there was a correlation between the loss of compound and their LogP.

Thank you to HESI for inviting Metrion to contribute to this important work.

Assessing Variability of hERG Data

Download
Recommended Publications
Latest Publications
Robust Sensory Neuron Phenotype Identified in Human iPSC-derived Sensory Neurons using Electrophysioloigcal Recordings

The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.

Validation of Antibody Toxin Fusions Against Sodium Channels

Using automated patch clamp technology, we evaluate the potency and selectivity of ten Nav1.7-selective arachnid peptide toxins, which have been fused to the C-terminus (Fc region) of human IgG1.

View All
Metrion is a contract research organisation (CRO) specialising in high-quality preclinical drug discovery services.
magnifier
linkedin facebook pinterest youtube rss twitter instagram facebook-blank rss-blank linkedin-blank pinterest youtube twitter instagram