| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
The primary cytotoxic component of TAS-102 is trifluridine (FTD). Trifluridine is a thymidine-based nucleoside analog that is incorporated into DNA in tumor cells following phosphorylation by thymidine kinase 1 (TK1). This incorporation into DNA leads to DNA dysfunction and inhibition of cell proliferation, which is the primary mechanism of action. Tipiracil hydrochloride (TPI) is an inhibitor of thymidine phosphorylase (TP), the enzyme that degrades trifluridine into its inactive metabolite (5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione). By inhibiting TP, tipiracil prevents the rapid degradation of trifluridine, maintaining adequate levels of trifluridine in the body and enhancing its bioavailability and cytotoxicity.
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| ln Vitro |
Trifluridine (FTD), a thymidine-based nucleoside analog, and tipiracil hydrochloride (TPI), an oral combination medication that increases the bioavailability of FTD by preventing thymidine phosphorylase (TP) from catabolizing it, make up TAS-102[1].
Trifluridine that has been phosphorylated is incorporated into DNA, causing DNA dysfunction and cell cycle arrest. Angiogenesis is inhibited and FTD degradation is inhibited by thymidine phosphorylase inhibitor. As a result, massive trifluridine incorporation into DNA and the activation of related DNA damage response pathways—which include cycle arrest during the G2/M-phase and Chk1 phosphorylation—are the outcomes of TAS-102 treatment[2]. In vitro, trifluridine is incorporated into DNA in tumor cells following phosphorylation by thymidine kinase 1. This incorporation leads to DNA dysfunction and inhibition of cell proliferation. Tipiracil is a potent inhibitor of thymidine phosphorylase, with an IC50 of 35 nM. It is selective for thymidine phosphorylase over uridine phosphorylase (UPase), thymidine kinase (TK), orotate phosphoribosyltransferase (OPRTase), and dihydropyrimidine dehydrogenase (DPD) (IC50s = >1,000 µM for all). |
| ln Vivo |
Due to the fast breakdown of FTD into its main metabolite, 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, the elimination half-life of FTD in humans following intravenous administration is extremely short (18 minutes). After oral administration alone, the plasma FTD level in monkeys is remarkably low, indicating extensive first-pass metabolism by the intestine and liver TPase. Oral administration is found to be made possible by the addition of TPI (tipiracil hydrochloride). By blocking TP, TPI increases the bioavailability of FTD by preventing its breakdown in the intestines and liver after oral administration. TP is an enzyme that catalyzes the phosphorolysis of FTD and other pyrimidine 2'-deoxynucleosides. The greatest antitumor activity is attained with a 1:0.5 molar ratio, according to studies conducted on human CRC tumor xenografts in mice. Similarly, studies conducted on mice and monkeys demonstrate that the maximum plasma concentration of FTD is nearly attained with the same ratio. Additionally, a good balance between toxicity and antitumor activity is produced by this ratio. When TPI is administered in addition to FTD, mice exhibit less toxicity. Because the primary mechanism of TAS-102 is unrelated to the primary metabolic enzymes of 5-FU, such as TS and OPRT, it can overcome acquired resistance to 5-FU. TAS-102 has proven effective in cancers that are resistant to 5-FU[1].
In vivo, TAS-102 is administered orally. Trifluridine is the cytotoxic component that causes damage to DNA, which can ultimately trigger cell death. Tipiracil prevents rapid breakdown of trifluridine, thereby maintaining adequate levels of the trifluridine in the body. The antitumor activity of TAS-102 is a result of the synergistic action of its two components. |
| Enzyme Assay |
The in vitro activity of TAS-102 is assessed using a combination of assays for its two components. The cytotoxicity of trifluridine is assessed in cancer cell lines using the MTT or colony formation assays. Cells are treated with various concentrations of trifluridine (typically ranging from 0.1 to 100 µM) for different time periods (e.g., 24-72 hours), and cell viability is measured. The incorporation of trifluridine into DNA can be assessed using radiolabeled trifluridine or by mass spectrometry. The inhibition of thymidine phosphorylase by tipiracil is assessed in cell-free enzyme assays. The enzyme is incubated with its substrate (thymidine) and varying concentrations of tipiracil, and the production of thymine is measured spectrophotometrically or by HPLC.
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| Cell Assay |
TAS-120 was applied to the cells in varying concentrations.
For cellular assays, the combination of trifluridine and tipiracil is tested in cancer cell lines. Cells are cultured in appropriate media (e.g., RPMI-1640 with 10% fetal bovine serum) and treated with various concentrations of the combination at the 1:0.5 M ratio. Cell viability is assessed using the MTT assay. The effect on DNA synthesis can be assessed by measuring the incorporation of [3H]thymidine or by using the BrdU incorporation assay. The induction of apoptosis can be assessed by measuring caspase activity or by flow cytometry using Annexin V staining. |
| Animal Protocol |
Male nude mice bearing KM12C, KM12C/5-FU, DLD-1, DLD-1/5-FU, and SC-2 cells
150 mg/kg/day p.o.; twice a day for 14 days In vivo, TAS-102 is administered orally to mice bearing human tumor xenografts. The compound is typically formulated in a vehicle such as 0.5% methylcellulose and administered at various doses (e.g., 50-200 mg/kg) once or twice daily. Tumor growth is monitored by measuring tumor volume over time. The antitumor efficacy is assessed by calculating the tumor growth inhibition (TGI) and the ratio of treated to control tumor volume (T/C). Pharmacodynamic studies can be performed by measuring the levels of trifluridine and its incorporation into DNA in tumor tissue. |
| ADME/Pharmacokinetics |
TAS-102 is administered orally. Trifluridine is rapidly metabolized by thymidine phosphorylase to its inactive metabolite, which is why tipiracil is co-administered to inhibit this degradation. Tipiracil itself is not absorbed systemically to a significant extent; it acts locally in the gastrointestinal tract and in the liver to inhibit thymidine phosphorylase, thereby increasing the bioavailability of orally administered trifluridine. The half-life of trifluridine is prolonged in the presence of tipiracil.
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| Toxicity/Toxicokinetics |
The toxicity profile of TAS-102 is primarily related to trifluridine, the cytotoxic component. Common side effects include myelosuppression (neutropenia, thrombocytopenia, anemia), gastrointestinal effects (nausea, vomiting, diarrhea, decreased appetite), and fatigue. Tipiracil, as a thymidine phosphorylase inhibitor, may contribute to the overall safety profile but is generally considered to have low systemic toxicity due to its limited absorption.
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| References | |
| Additional Infomation |
TAS-102 (marketed as Lonsurf) is an FDA-approved drug for the treatment of metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. It represents a successful example of a drug combination designed to enhance the efficacy of a nucleoside analog by inhibiting its metabolism. The development of TAS-102 highlights the importance of understanding drug metabolism and the potential of combination therapies to overcome resistance mechanisms.
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| Molecular Formula |
C19H23CL2F3N6O7
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|---|---|
| Molecular Weight |
575.3231
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| Elemental Analysis |
C, 39.67; H, 4.03; Cl, 12.32; F, 9.91; N, 14.61; O, 19.47
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| CAS # |
733030-01-8
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| Related CAS # |
70-00-8 (Trifluridie); 733030-01-8 (183204-72-0 (Tipiracil HCl)
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| Appearance |
White to off-white solid powder
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| SMILES |
ClC1C(N([H])C(N([H])C=1C([H])([H])N1/C(/C([H])([H])C([H])([H])C1([H])[H])=N/[H])=O)=O.Cl[H].FC(C1C(N([H])C(N(C=1[H])C1([H])C([H])([H])[C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])=O)=O)(F)F
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| InChi Key |
PLIXOHWIPDGJEI-OJSHLMAWSA-N
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| InChi Code |
InChI=1S/C10H11F3N2O5.C9H11ClN4O2.ClH/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7;10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11;/h2,5-7,16-17H,1,3H2,(H,14,18,19);11H,1-4H2,(H2,12,13,15,16);1H/t5-,6+,7+;;/m0../s1
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| Chemical Name |
4-hydroxy-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-(trifluoromethyl)pyrimidin-2(1H)-one compound with 5-chloro-6-((2-iminopyrrolidin-1-yl)methyl)pyrimidine-2,4-diol (1:1) hydrochloride
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| Synonyms |
TAS-102; TAS102; TAS 102; Trifluridine/tipiracil hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: ~100 mg/mL (~229.5 mM)
DMF: ~20 mg/mL (~45.9 mM) DMSO: 2.3~87 mg/mL (5.4~199.7 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (114.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Solubility in Formulation 2: 100 mg/mL (229.48 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7382 mL | 8.6908 mL | 17.3816 mL | |
| 5 mM | 0.3476 mL | 1.7382 mL | 3.4763 mL | |
| 10 mM | 0.1738 mL | 0.8691 mL | 1.7382 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04868773 | Active Recruiting |
Drug: Cabozantinib Drug: TAS-102 |
CRC Metastatic Cancer |
University of California, Irvine |
July 16, 2021 | Phase 1 |
| NCT04683965 | Active Recruiting |
Drug: TAS-102 Drug: Pemetrexed |
Colorectal Neoplasms | The First Affiliated Hospital with Nanjing Medical University |
January 1, 2021 | Phase 2 |
| NCT05600309 | Active Recruiting |
Drug: TAS-102 Drug: regorafenib |
Colorectal Cancer | Merck Sharp & Dohme LLC | June 14, 2022 | Phase 3 |
| NCT05064059 | Active Recruiting |
Drug: regorafenib Drug: TAS-102 |
Colorectal Cancer | Merck Sharp & Dohme LLC | November 10, 2021 | Phase 3 |
| NCT04776148 | Active Recruiting |
Drug: TAS-102 (trifluridine and tipiracil) Drug: regorafenib |
Colorectal Neoplasms | Merck Sharp & Dohme LLC | March 29, 2021 | Phase 3 |
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