title: SiDMAP: a metabolomics approach to assess the effects of drug candidates on the dynamic properties of biochemical pathways.
abstract: The postgenomic era in drug development is characterised by a need to describe and predict the functional actions of a given compound within the complex systems of the organism. Recent advances in analytical and computational techniques have given rise to a new and powerful tool for the measurement of biochemical pathways in cells, animals and humans. The stable isotope dynamic metabolic profiling (SiDMAP) assay measures the flow of molecules through complex metabolic pathways, rather than just measuring the gene or protein in isolation. Thus, the SiDMAP assay is a measurement of the phenotype in biology, disease and the treatment of disease. The SiDMAP assay differs from other static approaches in two key ways: i) SiDMAP measures the activity of pathways in fully intact systems, rather than just the component pieces of the system; and ii) SiDMAP measures molecular flux observed in the dimension of time, as apposed to measuring overall levels of metabolites in a system and then trying to predict functionality. These two features confer unparalleled sensitivity to the SiDMAP analysis and have allowed for the discovery of the activity of biochemical pathways important to a number of diseases, including cancer and the metabolic syndrome and how to best treat these diseases targeting the system of pathways. Thus, SiDMAP is a technology that can be widely used in the drug discovery and development process to better describe the biochemistry of disease states, determine the method of action of compounds, detect possible toxicity early in the drug development process, reposition compounds, develop biomarkers stratify patients and to enable Phase IV studies.
authors.affiliation: SiDMAP, 2990 S. Sepulveda Blvd. #300B, Los Angeles, CA 90064, USA. gmaguire@sidmap.com.
authors.forename: Greg
authors.initials: G
authors.lastname: Maguire
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Manheim
authors.forename: Laszlo
authors.initials: L
authors.lastname: Boros