hERG toxicity assessment: Useful guidelines for drug design
Résumé
All along the drug development process, one of the most frequent adverse side effects, leading
to the failure of drugs, is the cardiac arrhythmias. Such failure is mostly related to the capacity
of the drug to inhibit the human ether-à-go-go-related gene (hERG) cardiac potassium
channel. The early identification of hERG inhibition properties of biological active
compounds has focused most of attention over the years. In order to prevent the cardiac side
effects, a great number of in silico, in vitro and in vivo assays have been performed. The
main goal of these studies is to understand the reasons of these effects, and then to give
information or instructions to scientists involved in drug development to avoid the cardiac
side effects. To evaluate anticipated cardiovascular effects, early evaluation of hERG toxicity
has been strongly recommended for instance by the regulatory agencies such as U.S. Food
and Drug Administration (FDA) and European Medicines Agency (EMA). Thus, following an
initial screening of a collection of compounds to find hits, a great number of
pharmacomodulation studies on the novel identified chemical series need to be performed
including activity evaluation towards hERG. We provide in this concise review clear
guidelines, based on described examples, illustrating successful optimization process to avoid
hERG interactions as cases studies and to spur scientists to develop safe drugs.
Domaines
ChimieOrigine | Fichiers produits par l'(les) auteur(s) |
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