Monday, 23 May 2005

This presentation is part of: Pharmaceutical Profiling Posters

Strategies and Techniques of Major Metabolite Profiling for Structure Optimization in Drug Discovery

Mei-Yi Zhang, Teresa Kleintop, Natasha Kagan, and Edward Kerns. Wyeth Research, Princeton, NJ

Oral bio-availability is an important ADME property, if low, which may lead to failure of a drug candidate in development. High throughput in vitro metabolic stability screening assays have been widely used to identify such high clearance compounds in drug discovery. Early identification of the major metabolic pathways provides additional information to address the metabolism related liabilities. This poster describes the strategies and techniques for major metabolite profiling. Using our approach, the major metabolic pathways were identified at the physiologically relevant drug exposure concentrations. The metabolism-structure relationships were studied by profiling series analogues in parallel. The exact structure of major metabolites was determined using MS/MS and NMR with isolated metabolites. The study provides important information for discovery chemists to block metabolically labile spots on the molecules and design metabolically more stable compounds.

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