title: Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase             inhibitor library.
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.
authors: Sanford-Burnham Medical Research Institute, 10901                     North Torrey Pines Road, La Jolla, California                 92037, USA.
authors: Stefano
authors: S
authors: Tiziani
authors: Yunyi
authors: Y
authors: Kang
authors: Janet S
authors: JS
authors: Choi
authors: William
authors: W
authors: Roberts
authors: Giovanni
authors: G
authors: Paternostro
mesh_terms: D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000032:analysis*
chemical_list: D047428:Protein Kinase Inhibitors