Drug covalent binding study

Although in the past biotransformation to produce protein-reactive products has not been considered important in discovery toxicology studies, this situation appears to be changing. The limiting factor has been availability of radiolabeled drug to conduct appropriate covalent binding studies, but strategies have been proposed to overcome this obstacle [25],... 

Utility of Reactive Metabolite Trapping and Covalent Binding Studies in Drug Discovery... 

While covalent binding studies have an advantage over the reactive metabolite assay in that they provide a quantitative estimate of covalently bound drug to proteins and therefore an indirect measure of reactive metabolite formation, there are no studies to date which show a correlation between the extent of covalent binding and/or reactive metabolite formed and the probability that a drug is... 

ARE REACTIVE METABOLITE TRAPPING AND COVALENT BINDING STUDIES RELIABLE PREDICTORS OF TOXICITY POTENTIAL OF DRUG CANDIDATES ... 

Covalent Binding Studies with Radiolabeled Drug Candidates.522... 

In addition to the more fundamental limitations of the covalent binding studies to assess metabolic activation potential outlined above, there are also several practical issues that relate specifically to the lead optimization process in drug discovery that warrant discussion here. 

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