The combination drug tegafur/gimeracil/oteracil (trade name Teysuno, and TS-1 in Japan) is used for the treatment of advanced gastric cancer. It is also being developed for the treatment of hepatocellular carcinoma.
Mechanism of action
Tegafur is the actual chemotherapeutic agent. It is a prodrug of the active substance fluorouracil (5-FU).
Gimeracil inhibits the degradation of fluorouracil by reversibly blocking a dehydrogenase enzyme. This results in higher 5-FU levels and a prolonged half-life of the substance.
Oteracil mainly stays in the gut because of its low permeability, where it reduces the production of 5-FU by blocking the enzyme orotate phosphoribosyltransferase. Lower 5-FU levels in the gut result in a lower gastrointestinal toxicity.