NCI Drug Dictionary

The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.

dUTPase inhibitor TAS-114
An orally bioavailable inhibitor of both deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD), with potential antineoplastic adjuvant activity. Upon oral administration in combination with a prodrug of the pyrimidine antagonist 5-fluorouracil (5-FU), TAS-114 inhibits (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. This prevents first-pass metabolism of 5-FU, allowing oral administration of the 5-FU prodrug and increasing the efficacy of 5-FU. In addition, as a dUTPase inhibitor, TAS-114 enhances the antitumor activity of 5-FU by preventing the hydrolysis and breakdown of 5-fluoro-deoxyuridine triphosphate (FdUTP) and deoxyuridine triphosphate (dUTP), which are active metabolites of 5-FU. This promotes DNA polymerase-dependent incorporation of these antimetabolites into DNA and leads to DNA damage and tumor cell death. Co-administration with TAS-114 allows lower dosing of 5-FU prodrugs, which decreases 5-FU-related toxicity, while maintaining therapeutic levels of 5-FU at the tumor site. Check for active clinical trials using this agent. (NCI Thesaurus)

Code name:TAS-114