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Fluorouracil (Adrucil), a heterocyclic aromatic organic compound, is a potent anticancer agent widely used for the treatment of solid tumors, including breast cancer, ovarian cancer, head and neck cancer, and colon cancer. As an analogue of uracil, fluorouracil has a fluorine atom replacing the hydrogen atom at the C-5 position. Due to its similar chemical structure to DNA and RNA, fluorouracil and metabolites exert strong anticancer activities through incorporation into DNA and RNA and inhibition of thymidylate synthase (TS). Fluorouracil is metabolized into fluorodeoxyuridine monophosphate (FdUMP), which inhibits TS by forming a stable complex with it and subsequently suppresses the production of deoxythymidine monophosphate (dTMP), an essential enzyme involved in DNA replication and repair, leading to cytotoxicity and cell death.

Reference

[1].Ning Zhang, Ying Yin, Shen-Jie Xu and Wei-Shan Chen. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules 2008, 13, 1551-1569

[2].Michael D. Wyatt and David M. Wilson III. Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci. 2009; 66(5): 788-799