hERG toxicity assessment: Useful guidelines for drug design
| Autor: | Serge Mignani, Patrick Dallemagne, Christophe Rochais, Amanda Garrido, Alban Lepailleur |
|---|---|
| Přispěvatelé: | Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Universidade da Madeira (UMA) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject hERG Bioinformatics 01 natural sciences Food and drug administration 03 medical and health sciences Drug Discovery Humans [CHIM]Chemical Sciences Adverse effect 030304 developmental biology media_common Pharmacology 0303 health sciences Cardiotoxicity biology 010405 organic chemistry Chemistry Organic Chemistry General Medicine Ether-A-Go-Go Potassium Channels 0104 chemical sciences 3. Good health Drug development Drug Design Toxicity Practice Guidelines as Topic biology.protein |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, Elsevier, 2020, 195, pp.112290-. ⟨10.1016/j.ejmech.2020.112290⟩ |
| ISSN: | 0223-5234 1768-3254 |
| DOI: | 10.1016/j.ejmech.2020.112290⟩ |
| Popis: | 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-a-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. |
| Databáze: | OpenAIRE |
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