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Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase inhibitor library

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  • Stefano Tiziani

    (Sanford-Burnham Medical Research Institute)

  • Yunyi Kang

    (Sanford-Burnham Medical Research Institute)

  • Janet S. Choi

    (Sanford-Burnham Medical Research Institute)

  • William Roberts

    (Rady Children's Hospital, UCSD)

  • Giovanni Paternostro

    (Sanford-Burnham Medical Research Institute)

Abstract

Metabolism is altered in many highly prevalent diseases and is controlled by a complex network of intracellular regulators. Monitoring cell metabolism during treatment is extremely valuable to investigate cellular response and treatment efficacy. Here we describe a nuclear magnetic resonance-based method for screening of the metabolomic response of drug-treated mammalian cells in a 96-well format. We validate the method using drugs having well-characterized targets and report the results of a screen of a kinase inhibitor library. Four hits are validated from their action on an important clinical parameter, the lactate to pyruvate ratio. An eEF-2 kinase inhibitor and an NF-kB activation inhibitor increased lactate/pyruvate ratio, whereas an MK2 inhibitor and an inhibitor of PKA, PKC and PKG induced a decrease. The method is validated in cell lines and in primary cancer cells, and may have potential applications in both drug development and personalized therapy.

Suggested Citation

  • Stefano Tiziani & Yunyi Kang & Janet S. Choi & William Roberts & Giovanni Paternostro, 2011. "Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase inhibitor library," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1562
    DOI: 10.1038/ncomms1562
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