Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase inhibitor library
Open accessAbstract
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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NMR-based metabolomics can be used for quantification of metabolomic change in cells perturbed by drug treatments.
“NMR-based metabolomics can be used for the quantification of the metabolomic change in cells perturbed by drug treatments.142”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [142]
Data analysis identified four drugs having an impact on the ratio lactate to pyruvate.
“Subsequent data analysis led to the identification of four drugs having an impact on a crucial clinical parameter (ratio lactate to pyruvate).142”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [142]
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- Authors
- Tiziani, S., Kang, Y., Choi, J. S., Roberts, W., & Paternostro, G.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- University of California San Diego (US)
- Corresponding author
- Paternostro, Giovanni
- Venue
- Nature Communications
- Published
- 2011-11-22
- Volume
- 2
- Issue
- 1
- Pages
- 545-545
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5529142
- OpenAlex
- W2082904490
- Cited by
- 60
- References
- 61
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (0829891)
- National Institutes of Health (HL098053)
- National Institute on Aging (R21AG030685)
- National Heart, Lung, and Blood Institute (P01HL098053)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Keywords
- drug screening, cellular metabolism, metabolomics, kinase inhibitors, lactate/pyruvate ratio, NF-κB activation, MK2 inhibitors, protein kinase inhibitors, cancer cells, personalized treatment
- MeSH terms
- Cell Line, Drug Evaluation, Preclinical, Humans, Magnetic Resonance Spectroscopy, Protein Kinase Inhibitors
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