title: Systems biology, metabolic modelling and metabolomics in drug discovery and development.
abstract: Unlike signalling pathways, metabolic networks are subject to strict stoichiometric constraints. Metabolomics amplifies changes in the proteome, and represents more closely the phenotype of an organism. Recent advances enable the production (and computer-readable encoding as SBML) of metabolic network models reconstructed from genome sequences, as well as experimental measurements of much of the metabolome. There is increasing convergence between the number of human metabolites estimated via genomics ( approximately 3000) and the number measured experimentally. It is thus both timely, and now possible, to bring these two approaches together as an integrated (if distributed) whole to help understand the genesis of metabolic biomarkers, the progress of disease, and the modes of action, efficacy, off-target effects and toxicity of pharmaceutical drugs.
authors.affiliation: School of Chemistry, Faraday Building, The University of Manchester. PO Box 88, Manchester, M60 1QD, UK. dbk@manchester.ac.uk
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
mesh_terms: D003198:Computer Simulation; D017277:Drug Approval; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D023281:Genomics / Q000379:methods; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D049490:Systems Biology / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations