Molecular determinants of high-affinity drug binding to HERG channels.
Curr Opin Drug Discov Devel
; 6(5): 667-74, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-14579516
ABSTRACT
Human ether-a-go-go-related gene (HERG) subunits mediate a K+ current that is required for normal repolarization of the cardiac action potential. The unintentional inhibition of HERG currents by numerous medications results in prolongation of the QT interval, as measured on the electrocardiogram, and is associated with increased risk of patients suffering from life-threatening cardiac arrhythmias. QT interval prolongation is considered a major safety concern by worldwide drug regulatory bodies, and early detection of new compounds with this undesirable side effect has become an important objective for pharmaceutical companies. New studies are shedding light on the structural basis of drug binding and the gating-dependent repositioning of key residues in the inner cavity of HERG, which are responsible for the unusual sensitivity of HERG to pharmacological agents. Insights from these studies may help develop novel strategies to reduce the proarrhythmic potential of the next generation of drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Proteínas de Transporte de Cátions
/
Bloqueadores dos Canais de Potássio
/
Antiarrítmicos
Tipo de estudo:
Screening_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article