Minimizing the risk of chemically reactive metabolite formation of new drug candidates: implications for preclinical drug design.
Drug Discov Today
; 22(5): 751-756, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-27903430
ABSTRACT
Many pharmaceutical companies aim to reduce reactive metabolite formation by chemical modification at early stages of drug discovery. A practice often applied is the detection of stable trapping products of electrophilic intermediates with nucleophilic trapping reagents to guide rational structure-based drug design. This contribution delineates this strategy to minimize the potential for reactive metabolite formation of clinical candidates during preclinical drug optimization, exemplified by the experience at Roche over the past decade. For the majority of research programs it was possible to proceed with compounds optimized for reduced covalent binding potential. Such optimized candidates are expected to have a higher likelihood of succeeding throughout the development processes, resulting in safer drugs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Avaliação Pré-Clínica de Medicamentos
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Drug Discov Today
Ano de publicação:
2017
Tipo de documento:
Article