5-Fluorouracil (5-FU)

5-Fluorouracil (5-FU) is a uracil analog and a small molecule chemotherapeutic agent classified as an antimetabolite. It acts primarily as a suicide inhibitor of thymidylate synthase, thereby irreversibly blocking the conversion of deoxyuridine monophosphate (dUMP) to thymidine monophosphate (dTMP), which is necessary for DNA synthesis. In tumor cells, 5-FU is converted to three principal active metabolites: FdUMP, which inhibits TS; FdUTP, which is incorporated into DNA causing damage; and FUTP, which is incorporated into RNA, disrupting its processing and function. These processes lead to cell cycle arrest and apoptosis in rapidly dividing cancer cells. 5-FU is among the most widely used drugs for the treatment of colorectal, breast, gastrointestinal, head and neck, and many other cancers. Its major safety concern is severe toxicity in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, along with myelosuppression and mucosal toxicity[2][3][4][6].

Other names

FluorouracilUracil5-fluoro-EfudexFluoroplexFluracilFlurilNSC 19893Ro 2-9757ArumelCarzonalEffludermEfudixFluoroblastinFluriFUKecimetonTimazinU-8953Ulup5-Fluoro-2,4-pyrimidinedione5-Fluoropyrimidine-2,4-dione5-FtouracylAdrucilEfurix5-Fluoracil5-Fluor-2,4-dihydroxypyrimidin5-Fluor-2,4-pyrimidindiol5-FluoruracilFluracilumFtoruracilQueroplexCarac

Irreversible inhibition of thymidylate synthase (TS), blocking de novo synthesis of thymidine monophosphate (dTMP) needed for DNA synthesis - Conversion to active metabolites: fluorodeoxyuridine monophosphate (FdUMP), fluorodeoxyuridine triphosphate (FdUTP, incorporated into DNA), fluorouridine triphosphate (FUTP, incorporated into RNA) - RNA and DNA damage, disruption of DNA synthesis and repair, interference with RNA processing, induction of cell cycle arrest and p53-mediated apoptosis