Metabolomics (also known as metabonomics or metabolic profiling) has become an important tool for revealing unanticipated biochemical sequelae to administration of novel therapeutic agents. Within the pharmaceutical industry the technology has gained broad application from phenotyping transgenic models in early discovery through assessing bioreactor media in the manufacture of protein products. One of the earliest applications of the technology is still one of the most important - assessment of the unanticipated on and off target metabolic effects of candidate therapeutics in toxicology studies. However, clinical applications in patient stratification, efficacy and safety biomarker discovery and forward and reverse translational efforts are currently emerging as the new frontiers for the technology. While early metabolomics efforts focused on chemometric approaches, annotated metabolite lists have largely replaced the ubiquitous PCA plots of early efforts. It is not uncommon to measure several hundred metabolites across urine and plasma, even more if tissue extracts are assessed. Analytical approaches to routine metabolomic evaluation will be discussed along with specific examples covering the spectrum of applications of the technology in pharmaceutical development. In particular, metabolomics in early discovery efforts as a screening approach revealing unexpected off-target effects and unanticipated pharmacology of novel targets. Furthermore, metabolomics has proven invaluable in evaluating preclinical models and in reverse-translation approaches where clinical metabolomic data from target populations can be used to �grade� how well preclinical models mimic clinical physiology and pathology. Finally, metabolomics provides fresh insights into nettlesome toxicities, revealing unanticipated pathophysiology and the potential for novel biomarkers.

Metabolomics in the early assessment of drug safety and pharmaceutical development

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.