Metrion’s hERG channel screening expertise gives you the confidence to move forward with your discovery research
hERG Screening provides you with quick and reliable information regarding the potential cardiac liability of your compound due to binding to the hERG channel
Introduction to Metrion’s hERG Screening services
The cardiac rapid delayed rectifier potassium current (IKr), which is carried by an ion channel encoded by the human ether-à-go-go- related gene (hERG), plays an important role in ventricular repolarization. It is also integral in determining the QT-interval of the electrocardiogram; with QT-interval being the time taken for ventricular depolarisation and repolarisation.
It is widely acknowledged that hERG is highly susceptible to inhibition by a wide range of structurally diverse compounds. Inhibition of hERG is linked with prolongation of the QT-interval and the polymorphic ventricular tachycardia, Torsades de Pointes. Since the early 1990’s, a number of drugs have been withdrawn from the market due to their proarrhythmic liability.
Indeed, the association between drug-induced QT-interval prolongation and pharmacological blockade of hERG channels is sufficiently strong that hERG screening has been an important component of cardiac safety pharmacology for over 10 years. Furthermore, hERG screening will continue to be an important component of the proposed Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative, which will redefine the guidelines supporting the assessment of cardiac safety screening.
Metrion offers non-GLP hERG screening services using the QPatch automated gigaseal patch clamp platform.
- We offer four-point and eight-point concentration response hERG screening assays that are performed at room temperature.
- The compounds are applied in cumulative concentration-response format, with double additions of compound at each concentration.
- A concentration-response curve is also provided using the positive control reference compound, Verapamil.
The figure below shows a representative four-point concentration response assay using Verapamil.
Cardiac Safety Screening Resource Library
- CiPA hERG Milnes Kinetic Assay on Qpatch
- Nav1.5(late) Cardiac Safety Assay on Qpatch
- Nav1.5-ΔKPQ late INa current properties and pharmacology on the SyncroPatch 384i
- A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm.
- Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells.
- The Nav1.5 Late Current in WT and Nav1.5 ΔKPQ Mutant Channels: An Automated Patch Clamp LQT3 Electrophysiological Assay Comparison. Safety Pharmacology Society Virtual Meeting 2020.
- New CiPA Cardiac Ion Channel Cell Lines and Assays for In Vitro Proarrhythmia Risk Assessment. Japanese Safety Pharmacology Society Meeting, Tokyo, 2020
- Using new In Vitro Cardiac Ion Channel Assays and In Silico Models to Predict Proarrhythmia Risk with Automated Patch Clamp. Biophysical Society Annual Meeting, San Diego, 2020
- Development of an Impedance Based Screening Assay for Cardiac Safety and Cardiotoxicity Detection in Stem Cell derived Cardiomyocytes. Safety Pharmacology Society Annual Meeting, Barcelona, 2019
- Predicting Cardiac Proarrhythmic Risk Exclusively Using Automated Patch Clamp Data. Safety Pharmacology Society Annual Meeting, Barcelona, 2019
- New CiPA cardiac ion channel cell lines and assays for in vitro proarrhythmia risk assessment. Safety Pharmacology Society meeting, Washington DC, USA 2018.
- Assessment of human induced pluripotent stem cell-derived cardiomyocytes for evaluating drug-induced arrhythmias with multi-electrode array. Safety Pharmacology Society meeting, Washington DC, USA 2018.
- Refining in vitro QPatch cardiac ion channel QPatch and MEA iPSC cardiomyocyte assays for CiPA. SOT San Antonio 2018 poster Late Breaking 12: Safety Assessment: Pharmaceutical and Non-Pharmaceutical.
- CiPA update: Refining in vitro cardiac ion channel assays, in silico models and iPSC cardiomyocyte reagents for improved proarrhythmia risk prediction. SPS Vancouver September 2016 poster 0100.
- Human ventricular stem cell cardiomyocytes: validating in vitro assays and screening platforms for proarrhythmia risk prediction. SPS Vancouver September 2016 poster 0242.
- Human stem cell-derived cardiomyocytes: in vitro assays and screening platforms for exploring ventricular and atrial phenotypes. SPS Vancouver September 2016 poster 0247.
- Electrophysiological profiling of Axiogenesis CorV.4U iPSC-derived cardiomyocytes. Axiogenesis Workshop Cologne September 2016.
- Developing a package of in vitro human cardiac ion channel assays using automated patch clamp to predict clinical arrhythmia risk. SPS Prague September 2015.
- Presentation by Marc Rogers (Metrion CSO) at the June 2016 Sophion Ion Channel Modulation Symposium, Clare College, Cambridge (UK). CiPA update: in vitro cardiac ion channels screens, in silico models and stem cells iPS cardiomyocyte assays for pro-arrhythmia risk prediction.
- Presentation by Marc Rogers (Metrion CSO) at the September 2015 Safety Pharmacological Society, Prague. Using high quality HTS automated patch clamp data from human cardiac ion channels and in silico action potential modelling to cost-effectively predict QP prolongation and arrhythmia risk for CiPA.
Cardiac Safety Screening Technologies
- QPatch automated electrophysiology platform
- Patchliner automated electrophysiology
- Conventional manual patch clamp electrophysiology
- Plate-based impedance and microelectrode array techniques
- FlexStation plate-based imaging
Let’s work together
What are your specific ion channel screening requirements?
If you have any questions, or would like to discuss your project, we will put you directly in touch with a member of our scientific team. Contact us today to discover more.