TAS-114

TAS‑114 is an orally bioavailable small molecule that acts as a dual inhibitor of deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD). By inhibiting DPD, the enzyme responsible for the rapid catabolism of 5-fluorouracil (5-FU), TAS‑114 increases systemic exposure to 5-FU when used in combination with oral fluoropyrimidine prodrugs. As a dUTPase inhibitor, it prevents the breakdown of active metabolites FdUTP and dUTP, promoting their incorporation into DNA and enhancing DNA damage in tumor cells. This dual mechanism enhances antitumor activity while potentially reducing toxicity by allowing lower dosing of 5-FU prodrugs. Developed primarily for use in combination with fluoropyrimidines such as S‑1 or capecitabine, TAS‑114 has been investigated mainly for advanced solid tumors including gastric cancer and non-small cell lung cancer.

Other names

(R)-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-3-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy)propane-1-sulfonamideN-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide