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the claim
Fluorouracil inhibits thymidylate synthase to suppress DNA synthesis
the verdict
SUPPORTED
the evidence backs this
refutedsupported
the weight of evidence
4 sources for · 0 against

Multiple studies and reviews confirm that fluorouracil (5-FU) exerts its cytotoxic effects by inhibiting thymidylate synthase, which subsequently suppresses DNA synthesis and cancer cell proliferation.

Evidence for · 4
Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil
2024 · cited by 15
Paper 0 notes that 5-fluorouracil is best known for its misincorporation into DNA and inhibition of thymidylate synthase.
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The analysis

The retrieved literature consistently supports the established pharmacological mechanism of 5-fluorouracil, noting that its active metabolite inhibits thymidylate synthase to disrupt thymidine production and suppress DNA synthesis.

More for · 3
Structural aspects of the inhibition and catalytic mechanism of thymidylate synthase.
1995 · cited by 10
Paper 3 describes thymidylate synthase as a primary target for anticancer drugs like fluoropyrimidines due to its role in DNA precursor biosynthesis.
Bridging mechanism and design: modern medicinal chemistry approaches to thymidylate synthase inhibitors.
2026 · cited by 1
Paper 7 identifies thymidylate synthase as the central target in the action of classical antimetabolites such as fluoropyrimidines.
Everolimus destabilizes thymidylate synthase via suppressing its O-GlcNAcylation and sensitizes HER2-negative breast cancer to fluorouracil.
2026 · cited by 0
Paper 10 investigates thymidylate synthase as the direct target of 5-FU in breast cancer combination therapies.
Everything we examined (12)
  1. Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracilpeer-reviewedsupports
  2. Uracil: Failure To Restore DNA Synthesis While Relieving 5-Fluorouracil-Induced Inhibitionpeer-reviewedno side takennot shown: read and judged not to bear on this claim
  3. NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatmentpeer-reviewedno side takennot shown: read and judged not to bear on this claim
  4. Structural aspects of the inhibition and catalytic mechanism of thymidylate synthase.peer-reviewedsupports
  5. The mechanism underlying resistance to 5-fluorouracil and its reversal by the inhibition of thymidine phosphorylase in breast cancer cells.peer-reviewedno side takennot shown: read and judged not to bear on this claim
  6. Flavonoid-Based Combination Therapies and Nano-Formulations: An Emerging Frontier in Breast Cancer Treatment.peer-reviewedno side takennot shown: read and judged not to bear on this claim
  7. Gut microbiota as a hidden modulator of chemotherapy: implications for colorectal cancer treatment.peer-reviewedno side takennot shown: read and judged not to bear on this claim
  8. Bridging mechanism and design: modern medicinal chemistry approaches to thymidylate synthase inhibitors.peer-reviewedsupports
  9. Design, synthesis, molecular docking and cytotoxic evaluation of novel pyrimidine-based sulfonamide derivatives as potent anticancer agents: SAR insights and biological profiling.peer-reviewedno side takennot shown: read and judged not to bear on this claim
  10. Altered Pharmacodynamics of 1-(2-Tetrahydrofuryl)-5-fluorouracil by Pretreatment of Rats with Phenobarbital, Indomethacin, Diclofenac Sodium and Carbon Tetrachloridepeer-reviewedno side takennot shown: read and judged not to bear on this claim
  11. Everolimus destabilizes thymidylate synthase via suppressing its O-GlcNAcylation and sensitizes HER2-negative breast cancer to fluorouracil.peer-reviewedsupports
  12. Methotrexate inhibits the TEL-JAK2-STAT pathway through a folate metabolism-dependent mechanism in Ba/F3 cells.peer-reviewedno side takennot shown: read and judged not to bear on this claim
The paper trail · every fact has a biography
first checked05 Aug 2026
judged → SUPPORTED · 8205 Aug 2026
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