Potassium voltage-gated channel subfamily H member 2 (hERG1) (hERG1)

Potassium voltage-gated channel subfamily H member 2 (hERG1) is a pore-forming alpha subunit of the voltage-gated potassium channel that conducts the rapid delayed rectifier potassium current (IKr) in cardiac myocytes [1, 2]. This current is fundamental for the repolarization phase of the cardiac action potential, which allows the heart to relax and refill with blood [3]. While hERG1 is a therapeutic target for certain Class III anti-arrhythmic agents, it is most widely recognized as a critical safety liability in drug discovery [4]. Many structurally diverse drugs can inadvertently block the hERG channel, leading to a prolongation of the QT interval on an electrocardiogram and increasing the risk of Torsades de Pointes, a potentially fatal ventricular arrhythmia [3, 4]. Due to this risk, regulatory agencies require hERG safety testing for nearly all new drug candidates [4]. Additionally, hERG1 is frequently overexpressed in various human cancers, where it is thought to modulate cell membrane potential to favor tumor cell proliferation and metastasis [1, 2].

Other names

hERGKCNH2ERG1Kv11.1Ether-a-go-go-related gene potassium channel 1

Drugs typically act as pore blockers of the hERG channel, binding to the inner cavity of the channel to inhibit the rapid delayed rectifier potassium current (IKr), which prolongs the cardiac action potential duration [1, 3].