Multiple hERG channel blocking pathways: implications for macromolecules.
Trends Pharmacol Sci
; 45(8): 671-677, 2024 Aug.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Potasio
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Trends Pharmacol Sci
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido