Systems biology, metabolic modelling and metabolomics in drug discovery and development

• Published in: Drug discovery today Vol. 11; no. 23; pp. 1085 - 1092
• Main Author: Kell, Douglas B.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2006; Elsevier Science
• Subjects: Biological and medical sciences; Computer Simulation; Drug Approval; Drug Design; Drug-Related Side Effects and Adverse Reactions; General pharmacology; Genomics - methods; Humans; Medical sciences; Metabolic Networks and Pathways; Models, Biological; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - metabolism; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Proteomics - methods; Systems Biology - methods; Drug; Pharmacokinetics; Metabolism; Modeling; Metabonomics; Research and development
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2006.10.004

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 (∼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.