Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety.
HERG (human-ether-a-go-go-related gene) encodes for a cardiac potassium channel that plays a critical role in defining ventricular repolarization. Noncardiovascular drugs associated with a rare but potentially lethal ventricular arrhythmia (Torsades de Pointes) have been linked to delayed cardiac repolarization and block of hERG current. This brief overview will discuss the role of hERG current in cardiac electrophysiology, its involvement in drug-induced delayed repolarization, and approaches used to define drug effects on hERG current. In addition, examples of hERG blocking drugs acting differently (i.e., overt and covert hERG blockade due to multichannel block) together with the utility and limitations of hERG assays as tools to predict the risk of delayed repolarization and proarrhythmia are discussed.
Gintant
Gary A
GA
Deptartment of Integrative Pharmacology, Abbott Laboratories, Abbott Park, Illinois 60064-6119, USA. Gary.Gintant@abbott.com
Su
Zhi
Z
Martin
Ruth L
RL
Cox
Bryan F
BF
D000818:Animals; D000830:Animals, Laboratory; D015415:Biomarkers / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology*; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004364:Pharmaceutical Preparations / Q000145:classification; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
D015415:Biomarkers; D051638:Ether-A-Go-Go Potassium Channels; D004364:Pharmaceutical Preparations