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Role of Enzymes in Toxicity: Reactive Metabolites
Tuesday, November 13
2:00 pm – 4:30 pm
Symposium
ACPE #073-999-07-543-L04
Chemically reactive drug metabolites represent one of the major safety issues in the pharmaceutical industry as reactive intermediates are considered to play a role as mediators of drug-induced toxicities. Whereas identification of electrophilic species is nowadays relatively straightforward by appropriate in vitro and in vivo experiments, we are still lacking a mechanistic understanding of which reactive intermediates are likely to cause a toxic insult and which will be benign. Pharmaceutical companies have adopted strategies to minimize the potential for metabolic activation of drug candidates at the discovery/lead optimization phase. Research providing a deeper insight into mechanistic aspects of toxicities caused by reactive drug metabolites should enable the rational design of drug candidates with superior safety profiles and thus safer medicines for patients.
Moderators
Raimund M. Peter, Ph.D.
AstraZeneca
K. Sandy Pang, Ph.D.
University of Toronto
Drug Induced Liver Injury: Clinical Overview and Cellular Mechanisms
Neil Kaplowitz, M.D.
University of Southern California
Quinoids Formed from Selective Estrogen Receptor Modulators
Judy L. Bolton, Ph.D.
University of Illinois at Chicago
Factors Regulating Liver Susceptibility to Drug Protein Adducts
Mohammed Bourdi, Ph.D.
National Institutes of Health
Metabolic Activitation as a Component of an Integrated Safety Assessment
Axel Paehler, Ph.D.
F. Hoffman-La Roche, Ltd.