A history of the roles of cytochrome P450 enzymes in the toxicity of drugs.
Cytochrome P450
Drug-drug interactions
Drugs
Reactive intermediates
Toxicity
Toxicophores
Journal
Toxicological research
ISSN: 1976-8257
Titre abrégé: Toxicol Res
Pays: Singapore
ID NLM: 101483324
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
22
05
2020
revised:
22
05
2020
accepted:
11
06
2020
pubmed:
25
8
2020
medline:
25
8
2020
entrez:
25
8
2020
Statut:
epublish
Résumé
The history of drug metabolism began in the 19th Century and developed slowly. In the mid-20th Century the relationship between drug metabolism and toxicity became appreciated, and the roles of cytochrome P450 (P450) enzymes began to be defined in the 1960s. Today we understand much about the metabolism of drugs and many aspects of safety assessment in the context of a relatively small number of human P450s. P450s affect drug toxicity mainly by either reducing exposure to the parent molecule or, in some cases, by converting the drug into a toxic entity. Some of the factors involved are enzyme induction, enzyme inhibition (both reversible and irreversible), and pharmacogenetics. Issues related to drug toxicity include drug-drug interactions, drug-food interactions, and the roles of chemical moieties of drug candidates in drug discovery and development. The maturation of the field of P450 and drug toxicity has been facilitated by advances in analytical chemistry, computational capability, biochemistry and enzymology, and molecular and cell biology. Problems still arise with P450s and drug toxicity in drug discovery and development, and in the pharmaceutical industry the interaction of scientists in medicinal chemistry, drug metabolism, and safety assessment is critical for success.
Identifiants
pubmed: 32837681
doi: 10.1007/s43188-020-00056-z
pii: 56
pmc: PMC7431904
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1-23Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM118122
Pays : United States
Informations de copyright
© Korean Society of Toxicology 2020.
Déclaration de conflit d'intérêts
Conflict of interestThe authors have no conflict of interest to disclose.
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