The Trifluridine/tipiracil hydrochloride mixture (TAS-102) is an effective and orally active nucleoside antitumor agent. Comprised of a 1:0.5 molar ratio of alpha,alpha,alpha-tri-fluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI), TAS-102 exerts its antitumor effects predominantly through the inhibition of thymidylate synthase (TS) and by being incorporated into DNA[1].[2].
体内研究
When administered at 150 mg/kg/day orally twice a day for 14 days, it has been shown to prevent body weight loss and significantly reduce relative tumor volumes in colorectal and gastric cancer mouse models[2].
Trifluridine/tipiracil HCl mixture/盐酸曲氟尿苷 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HT29 cells
0, 1, 4, 8 µM
24, 48, 72 hours
FTD/TPI inhibits the viability and proliferation of HT29 cells in a dose-dependent manner
Cell Death Dis. 2025 Apr 5;16(1):255.
DLD1 cells
0, 1, 4, 8 µM
24, 48, 72 hours
FTD/TPI inhibits the viability and proliferation of DLD1 cells in a dose-dependent manner
Cell Death Dis. 2025 Apr 5;16(1):255.
HCT116
5 µM(IC50)
72 h
Evaluate the effect of AZD6738 combined with FTD on HCT116 cell viability. Results showed that AZD6738 combined with FTD significantly inhibited cell viability.
Oncol Rep. 2023 Mar;49(3):52.
HT29
70 µM(IC50)
72 h
Evaluate the effect of AZD6738 combined with FTD on HT29 cell viability. Results showed that AZD6738 combined with FTD significantly inhibited cell viability.
Oncol Rep. 2023 Mar;49(3):52.
CRC and PDAC p53Mut cell lines
0.5 μM
24-72 h
Evaluate DNA damage response to TAS102 in p53Mut cells, showing accumulation of DNA damage marker (γH2AX).
Cell Rep Med. 2024 Mar 19;5(3):101434.
HCT116 p53KO
0.5 μM
24-72 h
Evaluate DNA damage response to TAS102 in p53-deficient cells, showing accumulation of DNA damage (γH2AX).
Cell Rep Med. 2024 Mar 19;5(3):101434.
HCT116 p53WT
0.5 μM
24-72 h
Evaluate DNA damage response to TAS102 in p53WT cells, showing transient activation of p53-p21 axis and increase in DNA damage marker (γH2AX).
Cell Rep Med. 2024 Mar 19;5(3):101434.
iPSC-derived VSMCs (from HGPS patients)
5 µM
48 h
To screen compounds that can increase NAD+ levels. Results showed that Trifluridine significantly increased NAD+ levels by inhibiting PARP-1 activity and improved cell viability.
Cell Death Dis. 2024 Oct 2;15(10):723.
VSMCs from LmnaG609G/G609G mice
5 µM
48 h
To evaluate the effect of Trifluridine on NAD+ levels and cell viability. Results showed that Trifluridine significantly increased NAD+ levels by inhibiting PARP-1 activity and improved cell viability.
Cell Death Dis. 2024 Oct 2;15(10):723.
HT29 cells
0-16 μM
24-72 h
FTD/TPI inhibited the viability and proliferation of HT29 cells in a dose- and time-dependent manner.
Cell Death Dis. 2025 Apr 5;16(1):255.
DLD1 cells
0-16 μM
24-72 h
FTD/TPI inhibited the viability and proliferation of DLD1 cells in a dose- and time-dependent manner.
Cell Death Dis. 2025 Apr 5;16(1):255.
HCT116 cells
0-16 μM
24-72 h
FTD/TPI inhibited the viability and proliferation of HCT116 cells in a dose- and time-dependent manner.
Cell Death Dis. 2025 Apr 5;16(1):255.
RKO cells
0-16 μM
24-72 h
FTD/TPI inhibited the viability and proliferation of RKO cells in a dose- and time-dependent manner.
Cell Death Dis. 2025 Apr 5;16(1):255.
Trifluridine/tipiracil HCl mixture/盐酸曲氟尿苷 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NPG mice
Patient-derived xenograft models
Intraperitoneal injection
150 mg/kg
Once daily for 5 days as the first round, followed by a second round after a 2-day break
Combination therapy of FTD/TPI and SAS significantly inhibited tumor growth, reducing tumor volume and weight
Cell Death Dis. 2025 Apr 5;16(1):255.
BALB/cSlc-nu/nu mice
Esophageal squamous cell carcinoma xenograft model
Oral
200 mg/kg
Once daily for 3 weeks (TE-8) or 4 weeks (PDX)
To evaluate the antitumor effect of FTD/TPI and MK1775 combination therapy on esophageal squamous cell carcinoma xenograft models. Results showed that the combination therapy significantly suppressed tumor growth and increased γ-H2AX expression, indicating increased DNA double-strand breaks.
Cancer Sci. 2023 Dec;114(12):4664-4676
NPG mice
Patient-derived xenograft (PDX) models
Intraperitoneal injection
150 mg/kg
Once daily for 5 days as one round, total two rounds
Combination therapy of FTD/TPI and SAS significantly inhibited tumor growth in PDX models, reducing tumor volume and weight.
Cell Death Dis. 2025 Apr 5;16(1):255.
BALB/c nu/nu mice
HT29 xenograft model
Oral
200 mg/kg
Twice daily, 6-hour interval, for 3 weeks (5 days dosing, 2 days rest)
Evaluate the inhibitory effect of TAS-102 combined with AZD6738 on tumor growth in HT29 xenograft model. Results showed that the combination significantly inhibited tumor growth.
Oncol Rep. 2023 Mar;49(3):52.
Nude mice (BALB/cAJcl-nu/nu)
HCT116 p53-KO, p53-R175H, and p53-R248Q xenograft models
Oral
200 mg/kg
Once daily, days 1-5 and 8-12
To evaluate the anti-tumor effect of FTD/TPI on p53-GOF mutant xenografts, showing significant tumor growth suppression independent of p53 status.
Cell Death Discov. 2024 Jul 2;10(1):307.
Mice
LmnaG609G/G609G mouse model
Oral
150 mg/kg
Once daily for 4 weeks
Trifluridine treatment was able to alleviate aortic VSMCs loss and improve clinical signs of progeria.
Cell Death Dis. 2024 Oct 2;15(10):723.
Nude mice
Human colorectal cancer xenograft model
Oral
150 mg/kg
Twice daily for 14 days
To evaluate the antitumor effects of TAS-102 in combination with bevacizumab, cetuximab, or panitumumab. Results showed that the combination of TAS-102 and bevacizumab was significantly more effective than monotherapy in SW48 and HCT116 tumor models, with higher concentrations of phosphorylated FTD in tumors.
Oncol Rep. 2015 May;33(5):2135-42
SCID/CB17 mice
HT29 and MIAPACA2 tumor xenograft models
Oral gavage
50 mg/kg
5 days on, 2 days off
Evaluate anti-tumor efficacy of TAS102 combined with PARPi, showing significant inhibition of p53Mut tumor growth and extended survival.
Cell Rep Med. 2024 Mar 19;5(3):101434.
BALB/c mice
Colon cancer model
Oral
150 mg/kg
Once daily for 5 days
To evaluate the cytotoxic and pharmacodynamic effects of TAS-102 in vivo on colon cancer cells. Results showed TAS-102 significantly inhibited the growth of both cell lines (50%, P<0.01) and induced G2M-phase arrest and apoptosis.
Br J Cancer. 2007 Jan 15;96(1):61-6
Nude mice
Subcutaneous implantation model
Oral
15 mL/kg
Once a day for 1 week
Evaluate the antitumor effect of FTD on pancreatic cancer, results showed that the tumor volume increase was suppressed in the FTD group
Sci Rep. 2020 Jan 24;10(1):1138
SCID mice
LIM1215 and COL-01-JCK colon cancer patient-derived xenograft models
Orally
75 mg/kg
Twice daily for 2 weeks
To evaluate the in vivo antitumor effects of panitumumab and TAS-102 combination. Results showed that combination treatment caused significant tumor regression in LIM1215 and COL-01-JCK models.
Mol Oncol. 2017 Aug;11(8):1065-1077.
SCID/CB17 mice
MDA-MB-231 xenograft model
Oral gavage
50 mg/kg
5 days on, 2 days off
To evaluate the anti-tumor efficacy of TAS102 combined with PARP inhibitor, results showed significant inhibition of tumor growth and metastasis
Commun Biol. 2021 Jul 12;4(1):862
LmnaG609G/G609G mice
HGPS mouse model
Oral
150 mg/kg
Once daily for 4 weeks
To evaluate the effect of TAS-102 on aortic VSMCs loss and HGPS phenotype. Results showed that TAS-102 significantly reduced VSMCs loss and improved aortic disease phenotype.
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