The importance of glucuronidation for metabolism of xenobiotics in humans is illustrated by the abundance and broad tissue distribution of the enzymes, the diversity of substrates and reactions catalyzed, and the number of distinctive UGT enzymes and their genetic polymorphisms.
The involvement of UGTs in metabolism of new drug candidates will be presented as it underscores the enzymes’ importance from regulatory and safety perspectives. Basic biochemical characteristics of UGTs will be reviewed and examples of major forms of glucuronides formed in humans will be presented. Distinctive properties of acyl-glucuronides and their significance for drug-drug interactions will be highlighted. Factors contributing to underprediction of UGTs’ in vivo contributions to the metabolism of xenobiotics will also be covered. Laboratory approaches aimed at improving these predictions will be covered, as well.
Key Learning Objectives:
- Significance of UGT-mediated metabolism in drug development process
- Consequences of formation of acyl-glucuronides
- Underprediction of in vivo UGT-mediated metabolism
Who Should Attend:
- Research scientists and drug development leadership aiming for successful IND / NDA submission, needing to meet regulatory requests and expectations, desiring to formulate a development plan that mitigates risks of late-stage failure, or simply wanting to better understand the ADME properties and potential DDI risks of their compound.