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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 repolarisation and 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 Since the early 1990’s, a number of drugs have been withdrawn from the market due to their proarrhythmic liability.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.

hERG screening - ECG APD fig

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.

hERG promotion figs

In addition, Metrion also offers non-GLP hERG screening services on the manual patch clamp platform. Please contact us to learn more about our hERG screening services.

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