Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
Bioorg Med Chem Lett
; 26(16): 4003-6, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27397500
ABSTRACT
Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites. In order to reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, we developed a simple cell viability assay by combining a bioactivation system (human CYP3A4, CYP2D6 and CYP2C9) with Hep3B cells. We screened a series of drugs to explore structural motifs that may be responsible for CYP450-dependent activation caused by reactive metabolite formation, which highlighted specific liabilities regarding certain phenols and anilines.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Sistema Enzimático do Citocromo P-450
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos