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Nat Commun. 2011 Nov 22;2:545. doi: 10.1038/ncomms1562.

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

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Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.


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.

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