The hERG potassium channel is a voltage-gated cardiac channel that contributes to the rapid delayed rectifier current (IKr) required for ventricular action-potential repolarization. IKr blockade can delay repolarization and prolong the QT interval, increasing the risk of Torsade de Pointes, a potentially life-threatening cardiac arrhythmia.
The effects of hERG inhibition may be influenced by concurrent modulation of the late Nav1.5 current and Cav1.2. Drug-induced disturbance of Nav1.5 current can also contribute to severe arrhythmia, while inhibition of other potassium-current sources, including Kv4.3, KvLQT1/minK, and Kir2.1, may intensify or complement the contribution of hERG inhibition to QT-interval prolongation.
Our cardiac portfolio provides a comprehensive off-target profile of principal ion channels that influence ventricular action-potential duration. It also includes channels involved in heart-rate regulation, such as HCN2, HCN4, Kir3.1/Kir3.4, and Cav3.2; atrial repolarization, including Kv1.5; and the response to metabolic stress, including Kir6.2/SUR2A.
A comprehensive CiPA ion-channel panel supports systematic cardiac safety profiling.
Additional cardiac-relevant channels extend coverage beyond the core CiPA set.
Follow-up studies are also available to create an integrated package for profiling, risk assessment, and mechanism-of-action research.
Action-potential assays based on iPS-CMs and rabbit Purkinje-fiber preparations.
Langendorff perfusion assay.
Surface electrocardiogram assay using guinea pigs.
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