Deleterious effects of reactive metabolites

By S. Attia. Oxidative Medicine and Cellular Longevity, 2010

711 citations recorded by the source corpus.

A number of drugs have been withdrawn from the market or severely restricted in their use because of unexpected toxicities that become apparent only after the launch of new drug entities. Circumstantial evidence suggests that, in most cases, reactive metabolites are responsible for these unexpected toxicities. In this review, a general overview of the types of reactive metabolites and the consequences of their formation are presented. The current approaches to evaluate bioactivation potential of new compounds with particular emphasis on the advantages and limitation of these procedures will be discussed. Reasonable reasons for the excellent safety record of certain drugs susceptible to bioactivation will also be explored and should provide valuable guidance in the use of reactive-metabolite assessments when nominating drug candidates for development. This will, in turn, help us to design and bring safer drugs to the market.

Subfields: Pharmacology

View Paper: https://www.semanticscholar.org/paper/fd61346be798b01c42f2a4e1b2acb4c1c2b2229c

Citations in the corpus

• Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network (2016, neutral): “5,10 ,11,13 − 15 Despite these general rules, it remains a challenge to predict the reactivity of small molecules and their likelihood for modifying DNA and proteins.”