The hERG potassium channel as a therapeutic target.
The hERG (human ether-à-go-go-related gene) potassium channel has elicited intense scientific interest due to its counter-intuitive kinetics and its association with arrhythmia and sudden death. hERG blockade is involved in both antiarrhythmic pharmacotherapy and the pathogenesis of familial and acquired long QT syndrome (LQTS). Short QT syndrome (SQTS), muscular atrophy and many forms of cancer have also been associated with hERG as a target. Molecular models of both the channel and its blocker pharmacophores exist, revealing methods to design hERG liability out of potential drug molecules. Future developments will synthesise preclinical data on hERG with other criteria to determine net arrhythmogenic risk. Also, the molecular actions of hERG and its genetics will be elucidated in detail to allow clinical risk reduction.
Witchel
Harry J
HJ
University of Bristol, School of Medical Sciences, Department of Physiology, Bristol, BS8 1TD, UK. harry.witchel@bristol.ac.uk
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D012307:Risk Factors
D000889:Anti-Arrhythmia Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers