CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

@article{Almqvist2016CETSASI,
  title={CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil},
  author={Helena Almqvist and Hanna Axelsson and R. Jafari and Chen Dan and Andr{\'e} Mateus and M. Haraldsson and A. Larsson and Daniel Martinez Molina and P. Artursson and T. Lundb{\"a}ck and P. Nordlund},
  journal={Nature Communications},
  year={2016},
  volume={7}
}
Target engagement is a critical factor for therapeutic efficacy. [...] Key Result The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement.Expand
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