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Metabonomics: a platform for studying drug toxicity and gene function

Abstract

The later that a molecule or molecular class is lost from the drug development pipeline, the higher the financial cost. Minimizing attrition is therefore one of the most important aims of a pharmaceutical discovery programme. Novel technologies that increase the probability of making the right choice early save resources, and promote safety, efficacy and profitability. Metabonomics is a systems approach for studying in vivo metabolic profiles, which promises to provide information on drug toxicity, disease processes and gene function at several stages in the discovery-and-development process.

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Figure 1: Relating the real world to the 'omics' world.
Figure 2: Effect of time in toxicological studies.
Figure 3: A functional NMR spectrum of rat urine.
Figure 4: Metabonomic detection of liver and kidney toxicity.
Figure 5: Principal components analysis (PCA) of rat renal papillary damage.
Figure 6: Integrated metabonomics.

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Acknowledgements

We thank I. Wilson, (AstraZeneca Pharmaceuticals, UK), J. Everett, (Pfizer Global Research, UK) and D. Robertson (Pfizer Global Research, USA) for helpful discussions on the philosophy of metabonomics. We are grateful to M. Spraul and Bruker Analytik GmbH, Germany, for help with many metabonomics projects. Particular thanks are due to H. Antti, A. Nicholls, C. Gavaghan and J. Bundy for data collection and help with data processing. We thank J. Azmi for her help with the α-naphthylisothiocyanate data and analysis. We also thank The Engineering and Physical Sciences Research Council, the Medical Research Council, the Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council for funding this and related work over many years.

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Correspondence to Jeremy K. Nicholson.

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Nicholson, J., Connelly, J., Lindon, J. et al. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 1, 153–161 (2002). https://doi.org/10.1038/nrd728

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