TAS-114

TAS-114 is a dual dUTPase/dihydropyrimidine dehydrogenase (DPD) inhibitor, can improving the therapeutic efficacy of fluoropyrimidine[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

dUTPase, DPD

TAS-114 (1-10 μM; 72 hours) increases the cytotoxicity of 5-Fluorouracil (5-FU) and 5-FU,2′-deoxy-5-fluorouridine (FdUrd) against various cancer cell lines in dose-dependent manner[1]. Cell Cytotoxicity Assay[1] Cell Line: HeLa, NUGC-4, NCI-H441, HT-29, CFPAC-1, and MCF-7 cell lines Concentration: 72 hours Incubation Time: 1 μM, 3 μM, and 10 μM Result: Clearly increased the cytotoxicity of FdUrd and 5-FU against various cancer cell lines in dose-dependent manner.

TAS-114 (37.5-1,200 mg/kg/day; orally; 1-14 days) increases the antitumor activity of 5-FU when co-administers with Capecitabine (539 mg/kg/day) in mice[1]. Animal Model: BALB/c nude mice with MX-1 human breast cancer xenografts[1] Dosage: 37.5 to 1,200 mg/kg/day Administration: Orally; daily; 1-14 days Result: Decreased the tolerable doses of Capecitabine (539 mg/kg/day) in a dose-dependent manner in mice.

[1]. Yano W, et al. TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy. Mol Cancer Ther. 2018 Aug;17(8):1683-1693.