Thymidylate synthase–fluorodeoxyuridylate–folate ternary complex (TS–FdUMP–folate complex)

The "TS–FdUMP–folate complex" is a covalent ternary intermediate formed when the enzyme **thymidylate synthase (TS)** reacts with the cytotoxic metabolite **fluorodeoxyuridylate (FdUMP)**, in the presence of a folate cofactor (typically *5,10-methylene tetrahydrofolate*). FdUMP, derived from the prodrug 5-fluorouracil (5-FU), acts as a suicide inhibitor: it forms a stable covalent bond with TS and the cofactor, irreversibly blocking TS function[1][4][5][6]. Since TS catalyzes the methylation of dUMP to dTMP, its inhibition leads to thymidine nucleotide pool imbalance, DNA synthesis arrest, and tumor cell death. This mechanism underlies the clinical efficacy of 5-FU, capecitabine, and related drugs in cancer chemotherapy[1][4][6]. Diagnostic antibodies and assays can detect this complex in tumor tissue to monitor drug action and patient response[1].

Other names

TS–FdUMP–CH2THF complexthymidylate synthase ternary inhibitory complexTS-F (in some literature)5FU-modified TS

Irreversible (suicide) inhibition of thymidylate synthase via covalent ternary complex formation with FdUMP and 5,10-methylene tetrahydrofolate, preventing dTMP and thus DNA synthesis[1][4][5][6]