Role of UDP-Glucuronosyltransferases (UGTs) in Drug Metabolism and Drug-Drug Interactions
Presenter: Maciej Czerwinski, Ph.D., XenoTech Director of Scientific Consulting
Abstract:
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, as well as a 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 concepts discussed in this webinar will include:
- Significance of UGT-mediated metabolism in drug development process
- Consequences of formation of acyl-glucuronides
- Underprediction of in vivo UGT-mediated metabolism
About the Presenter:
Dr. Maciej Czerwinski serves as a Director in the Scientific Consulting department at XenoTech. He received his Ph.D. from the University of Maryland at Baltimore Medical School in the Department of Pathology. Dr. Czerwinksi conducted his doctoral thesis research in the Laboratory of Dr. Frank Gonzalez at the National Cancer Institute in Bethesda, followed by a post-doc at the Department of Pharmaceutics, the University of Washington in Seattle. He has been with XenoTech since 1999 and guides the development of products and services for the in vitro analysis of drug safety. Dr. Czerwinski designed a patented method to analyze the in vitro cytokine-mediated drug-drug interactions between biologics and small molecule drugs, and he is also the inventor of XenoTech’s CryostaX single-freeze pooled hepatocytes.
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