Fluorouracil inhibits thymidylate synthase to suppress DNA synthesis
Is it true that Fluorouracil inhibits thymidylate synthase to suppress DNA synthesis?
Yes. 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.
Verdict: SUPPORTED · 4 sources for, 0 against · Last checked
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.
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Chatterjee, S., Naeli, P., Onar, O., Simms, N., Garzia, A., Hackett, A. P., Coyle, K., Snell, P. H., McGirr, T., Sawant, T. N., Dang, K., Stoichkova, Z. V., Azam, Y., Saunders, M., Braun, M., Alain, T., Tuschl, T., McDade, S., Longley, D. B., Gkogkas, C. G., Adrain, C., Knight, J. R. P., & Jafarnejad, S. M. (2024). Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil. doi.org. https://doi.org/10.1093/nar/gkae849
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Hardy, L. W. (1995). Structural aspects of the inhibition and catalytic mechanism of thymidylate synthase.. doi.org. https://doi.org/10.18388/abp.1995_4891
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AA, A., ME, E., TA, Y., AO, A. K., & SS, H. (2026). Bridging mechanism and design: modern medicinal chemistry approaches to thymidylate synthase inhibitors.. doi.org. https://doi.org/10.1039/d5ra08381h
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XT, J., H, G., S, W., L, W., Z, C., LL, W., J, W., M, Z., N, L., W, Y., Y, L., L, J., Y, L., S, L., Q, S., J, L., K, Q., Q, W., X, Y., Z, Y., Y, C., Y, W., & Q, L. (2026). Everolimus destabilizes thymidylate synthase via suppressing its O-GlcNAcylation and sensitizes HER2-negative breast cancer to fluorouracil.. doi.org. https://doi.org/10.1038/s41419-026-08715-z
What does the evidence say?
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.
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