| 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 | |||
| 1g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
thymidine phosphorylase
Tipiracil HCl's primary target is the enzyme thymidine phosphorylase (TP). It is a selective inhibitor of TP, with an IC50 of 35 nM. It is highly selective for TP over other enzymes involved in pyrimidine metabolism, including uridine phosphorylase (UPase), thymidine kinase (TK), orotate phosphoribosyltransferase (OPRTase), and dihydropyrimidine dehydrogenase (DPD) (IC50s = >1,000 µM for all). By inhibiting TP, tipiracil prevents the breakdown of trifluridine into its inactive metabolite, thereby maintaining effective concentrations of trifluridine in the blood. |
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| ln Vitro |
Tipiracil hydrochloride suppresses the growth of endothelial cells and possesses anti-angiogenic properties [1]. FTD is broken down by the strong thymidine phosphorylase enzyme found in tipiracil hydrochloride [2].
In vitro, Tipiracil HCl is a potent inhibitor of thymidine phosphorylase, with an IC50 of 35 nM. It is selective for TP over other enzymes involved in pyrimidine metabolism. By inhibiting TP, it can increase the concentration of thymidine in cancer cells, leading to DNA damage and cell death. |
| ln Vivo |
In vivo, Tipiracil HCl is used in combination with trifluridine as TAS-102 for the treatment of colorectal cancer. It inhibits the degradation of trifluridine by thymidine phosphorylase, ensuring its bioavailability and enhancing its anticancer potential. It has also been studied for its potential to attenuate thrombosis without increasing the risk of bleeding in mice.
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| Enzyme Assay |
The in vitro activity of Tipiracil HCl is assessed using cell-free enzyme assays. Thymidine phosphorylase is incubated with its substrate (thymidine) and varying concentrations of Tipiracil HCl. The production of thymine, which results from the phosphorolytic cleavage of thymidine, is measured spectrophotometrically or by HPLC. The IC50 is determined as the concentration of Tipiracil HCl required to inhibit 50% of the enzyme activity. The selectivity of Tipiracil HCl for TP over other enzymes (e.g., UPase, TK, OPRTase, DPD) is assessed using similar enzyme assays with the respective substrates.
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| Cell Assay |
For cellular assays, the effect of Tipiracil HCl on the stability of trifluridine is assessed in cancer cell lines. Cells are treated with trifluridine in the presence or absence of Tipiracil HCl. The concentration of trifluridine and its metabolites in the culture medium and cell lysates is measured by HPLC or mass spectrometry. The cytotoxicity of trifluridine in the presence of Tipiracil HCl is assessed using the MTT or colony formation assays. Cells are treated with various concentrations of trifluridine and Tipiracil HCl (at a 1:0.5 M ratio) for different time periods, and cell viability is measured.
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| Animal Protocol |
In vivo, Tipiracil HCl is administered orally in combination with trifluridine. Its efficacy is evaluated in mouse xenograft models of human tumors. The compound is formulated in a suitable vehicle and administered at various doses. Tumor growth is monitored over time. The pharmacokinetic profile of trifluridine is assessed in the presence and absence of Tipiracil HCl by measuring plasma concentrations of trifluridine and its metabolites.
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| ADME/Pharmacokinetics |
Tipiracil HCl is administered orally in combination with trifluridine. It is not significantly absorbed systemically; it acts locally in the gastrointestinal tract and in the liver to inhibit thymidine phosphorylase. This local action prevents the degradation of trifluridine during the first pass through the gut and liver, thereby increasing the oral bioavailability of trifluridine.
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| Toxicity/Toxicokinetics |
Tipiracil HCl is generally well-tolerated. As a thymidine phosphorylase inhibitor, its toxicity is primarily related to its role in enhancing the exposure to trifluridine, the cytotoxic component of TAS-102. Common side effects of the combination are related to trifluridine and include myelosuppression and gastrointestinal effects. Tipiracil HCl itself has a low toxicity profile due to its limited systemic absorption.
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| References | |
| Additional Infomation |
Tipiracil hydrochloride is a hydrochloride salt prepared by reacting tilpyrimidine with an equimolar amount of hydrochloric acid. It is used in combination with the nucleoside metabolism inhibitor trifluorouridine for the treatment of advanced/recurrent unresectable colorectal cancer. It has antitumor activity and is also an EC 2.4.2.4 (thymidine phosphorylase) inhibitor. It is a hydrochloride and imine salt containing tilpyrimidine (1+) ions.
Tipiracil HCl is a key component of the FDA-approved drug TAS-102 (Lonsurf) for the treatment of metastatic colorectal cancer. Its development as a thymidine phosphorylase inhibitor was a critical step in enabling the oral administration of trifluridine, which would otherwise be rapidly degraded in the gastrointestinal tract and liver. The combination of a nucleoside analog with a metabolism inhibitor is a successful strategy that has been applied in other drug development programs as well. |
| Molecular Formula |
C9H12CL2N4O2
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|---|---|
| Molecular Weight |
279.12318
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| Exact Mass |
278.033
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| Elemental Analysis |
C, 38.73; H, 4.33; Cl, 25.40; N, 20.07; O, 11.46
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| CAS # |
183204-72-0
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| Related CAS # |
Trifluridine/tipiracil hydrochloride mixture;733030-01-8;Tipiracil;183204-74-2
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| PubChem CID |
9903778
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| Appearance |
White to off-white solid powder
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| LogP |
1.953
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
404
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| Defined Atom Stereocenter Count |
0
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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]
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| InChi Key |
KGHYQYACJRXCAT-UHFFFAOYSA-N
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| InChi Code |
nChI=1S/C9H11ClN4O2.ClH/c10-7-5(12-9(16)13-8(7)15)4-14-3-1-2-6(14)11;/h11H,1-4H2,(H2,12,13,15,16);1H
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| Chemical Name |
5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione;hydrochloride
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| Synonyms |
Lonsurf; TAS-1-462; MA-1 MA1Tipiracil HCl; TPI; TAS-102; TAS102
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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) |
Water: ~56 mg/mL (~200.6 mM)
DMSO: ~16 mg/mL (~57.3 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5827 mL | 17.9134 mL | 35.8269 mL | |
| 5 mM | 0.7165 mL | 3.5827 mL | 7.1654 mL | |
| 10 mM | 0.3583 mL | 1.7913 mL | 3.5827 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 |
| NCT03317119 | Active Recruiting |
Drug: Trametinib Drug: Trifluridine and Tipiracil Hydrochloride |
RAS Family Gene Mutation Metastatic Rectal Carcinoma |
City of Hope Medical Center | April 11, 2018 | Phase 1 |
| NCT03981614 | Active Recruiting |
Drug: Binimetinib Drug: Palbociclib |
Unresectable Carcinoma Metastatic Colorectal Carcinoma |
Academic and Community Cancer Research United |
October 29, 2019 | Phase 2 |
| NCT04097028 | Active Recruiting |
Drug: Oxaliplatin Drug: Trifluridine and Tipiracil Hydrochloride |
Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 |
Roswell Park Cancer Institute | December 20, 2019 | Phase 2 |
| NCT04109924 | Active Recruiting |
Drug: Irinotecan Biological: Bevacizumab |
Stage III Colon Cancer AJCC v8 Stage III Colorectal Cancer AJCCv8 |
Roswell Park Cancer Institute | December 27, 2019 | Phase 2 |
| NCT04294264 | Active Recruiting |
Drug: Oxaliplatin Drug: Trifluridine and Tipiracil Hydrochloride |
Stage IV Colon Cancer AJCC v7 Recurrent Colon Carcinoma |
Rutgers, The State University of New Jersey |
February 12, 2019 | Phase 2 |
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