Figure 1
The mode of action of S-1. S-1 is composed of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (gimestat [CDHP]), and oteracil potassium (Oxo) in a molar ratio of 1 : 0.4 : 1 to enhance the oral efficacy of FT, a prodrug of 5-fluorouracil (5-FU). CDHP inhibits the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme that degrades 5-FU, with about 180-fold more potency than uracil. Oxo is distributed in the gastrointestinal tract at a high concentration following oral administration, and it prevents phosphorylation (i.e., activation) of 5-FU by inhibiting the effect of orotate phosphoribosyl transferase (OPRT).
