Progress in research on metabolic pathways,toxicogenic mechanisms and detection methods of drug-reactive metabolites
FENG Wei-li
LIU Li
DENG Yi-fang
Abstract：Drug-reactive metabolites are reactive intermediates formed during catalytic reactions of drugs by metabolizing enzymes,which are electrophilic and can covalently bind to nucleophilic groups in biological macromolecules such as DNA or proteins to produce toxicity.A detailed understanding of the toxicogenic mechanisms and easy activation sites of drug-reactive metabolites is important in the screening of reactive metabolites,the structural design of drug candidates,and reduction of drug toxicity.In this paper,we reviewed some drugs with reactive metabolites detected in vivo or in vitro,classified them according to their binding targets and the types of reactive metabolites,discussed their mechanisms of toxicity,located the susceptible activation sites,and briefly described the methods for detecting reactive metabolites.
Keywords：reactive metabolitesprotein covalent bindingDNA covalent bindingmechanisms of drug toxicitydetection methods
Publication Date：2025-11-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：15( 2408-2422 )