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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-09

AUTHORS

Stefano Tiziani, Yunyi Kang, Janet S. Choi, William Roberts, Giovanni Paternostro

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. More... »

PAGES

545

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms1562

    DOI

    http://dx.doi.org/10.1038/ncomms1562

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1014830466

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22109519


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