Multiple hERG channel blocking pathways: implications for macromolecules.
Trends Pharmacol Sci
; 2024 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-39043501
ABSTRACT
Numerous non-cardiovascular drugs have a potential to induce life-threatening torsades de pointes (TdP) ventricular cardiac arrhythmias by blocking human ether-à-go-go-related gene (hERG) currents via binding to the channel's inner cavity. Identification of the hERG current-inhibiting properties of candidate drugs is performed focusing on binding sites in the channel pore. It has been suggested that biologicals have a low likelihood of hERG current inhibition, since their poor diffusion across the plasma membrane prevents them from reaching the binding site in the channel pore. However, biologicals could influence hERG channel function by binding to 'unconventional' noncanonical binding sites. This Opinion gives an overview on noncanonical blockers of hERG channels that might be of relevance for the assessment of the possible torsadogenic potential of macromolecular therapeutics.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Trends Pharmacol Sci
Ano de publicação:
2024
Tipo de documento:
Article