The hERG K+ channel: target and antitarget strategies in drug development.
The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.
Raschi
Emanuel
E
Department of Pharmacology, University of Bologna, Via Irnerio, 48, I-40126 Bologna BO, Bologna, Italy.
Vasina
Valentina
V
Poluzzi
Elisabetta
E
De Ponti
Fabrizio
F
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D016171:Torsades de Pointes / Q000188:drug therapy
D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers