Reactive metabolite (semicarbazide trapping (SCA), liver microsomes, human) - US

Background Information:

A leading cause of drug attrition, warnings and market withdrawals is drug mediated hepatotoxicity resulting from biotransformation. Biotransformation can result in covalent modification of DNA and cellular proteins causing drug-induced toxicities including mutagenicity, genotoxicity and idiosyncratic toxicity. Idiosyncratic toxicity may rely heavily on the formation of short-lived reactive metabolites which contain electrophilic groups that can covalently bind to nucleophilic moieties in proteins to form toxic adducts. Drug conjugated proteins and peptides can lose functionality, accumulate or generate an active immune response. Reactive metabolite formation in drug candidates has potential for toxicity as well as adverse drug reactions including Drug-Drug Interactions (DDIs) and Drug Induced Liver Injury (DILI). Major clinical liabilities can be prevented with structural modification or early termination in drug discovery programs with early in-vitro detection of reactive metabolites. Given this scenario, Eurofins developed a new qualitative in-vitro cocktail method to evaluate formation of reactive metabolites for de-risking lead therapeutic compounds or to troubleshoot adverse events in later stage programs.

Organism:

Human

Construct Details:

Microsomes