DNA synthesis pathway via fluoropyrimidine metabolism

The "DNA synthesis pathway via fluoropyrimidine metabolism" is not a single molecular target but rather refers to a network of enzymatic reactions involved in the activation and breakdown of fluoropyrimidine drugs such as 5-fluorouracil. The main cytotoxic effect arises from conversion of these drugs into active metabolites like fluorodeoxyuridine monophosphate (FdUMP), which inhibits the enzyme thymidylate synthase. This inhibition disrupts de novo DNA synthesis by blocking dTMP production, ultimately impairing cell proliferation. Key enzymes involved include thymidylate synthase, uridine phosphorylase, and dihydropyrimidinase. Variations or deficiencies in these enzymes can influence both drug efficacy and toxicity profiles. Expression levels of certain proteins—such as BCRP—can serve as biomarkers for drug resistance or sensitivity in cancers treated with fluoropyrimidines. This entry is considered incorrect as a therapeutic target because it describes an entire metabolic/drug action pathway rather than a specific molecular entity suitable for direct pharmacological targeting.

Other names

Fluoropyrimidine metabolism pathway5-Fluorouracil metabolic pathwayPyrimidine salvage and synthesis pathway (in context of fluoropyrimidines)

Inhibition of thymidylate synthase by FdUMP, leading to impaired DNA synthesis