| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
As a 5-fluorouracil derivative, 1-Acetyl-3-o-toluyl-5-fluorouracil functions as a nucleoside antimetabolite, exerting its antitumor effects primarily through the inhibition of thymidylate synthase (TS), a key enzyme in DNA synthesis . Following oral administration, the compound is activated and metabolized to release the active 5-FU moiety, which subsequently interferes with pyrimidine nucleotide synthesis and incorporates into RNA and DNA, leading to disrupted nucleic acid function and induction of apoptosis in rapidly dividing cancer cells.
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| ln Vitro |
Specific in vitro cytotoxicity data for 1-Acetyl-3-o-toluyl-5-fluorouracil is limited in the available literature. However, based on its structural classification as a nucleoside antimetabolite analog, the compound is expected to demonstrate antiproliferative activity against various tumor cell lines through mechanisms involving thymidylate synthase inhibition and disruption of nucleic acid metabolism .
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| ln Vivo |
On solid tumors of the MH134 type, oral administration of 1-acetyl-3-o-toluoyl-5-fluorouracil shows a notable effect that is greater than subcutaneous injection of the same drug. Oral administration of 1-acetyl-3-o-toluoyl-5-fluorouracil at a dose of 0.2 mmol/kg/d was found to have anticancer activity similar to subcutaneous administration of the same dose of 5-fluorouracil. When 1-acetyl-3-o-toluoyl-5-fluorouracil is administered orally, the amount of the weight loss in the thymus and the size of the weight gain in the spleen are less than when 5-fluorouracil (0.2 mmol/kg/day) is injected subcutaneously [1].
In vivo studies using murine hepatoma MH134 solid tumor models have demonstrated that oral administration of 1-Acetyl-3-o-toluyl-5-fluorouracil exhibits remarkable antitumor effects, with efficacy comparable to subcutaneous administration of 5-FU at the same dose of 0.2 mmol/kg/day . Notably, the oral administration route showed even more marked effects compared to subcutaneous administration of the compound itself . Additionally, A-OT-Fu demonstrated a favorable toxicity profile, with lower decreases in thymus weight and smaller increases in spleen weight following oral administration at any tested dose compared to subcutaneous 5-FU treatment (0.2 mmol/kg/day), indicating reduced immunosuppressive effects . In vivo studies using murine hepatoma MH134 solid tumor models have demonstrated that oral administration of 1-Acetyl-3-o-toluyl-5-fluorouracil exhibits remarkable antitumor effects, with efficacy comparable to subcutaneous administration of 5-FU at the same dose of 0.2 mmol/kg/day . Notably, the oral administration route showed even more marked effects compared to subcutaneous administration of the compound itself . Additionally, A-OT-Fu demonstrated a favorable toxicity profile, with lower decreases in thymus weight and smaller increases in spleen weight following oral administration at any tested dose compared to subcutaneous 5-FU treatment (0.2 mmol/kg/day), indicating reduced immunosuppressive effects . |
| Enzyme Assay |
Specific non-cellular enzyme/receptor binding assay protocols for 1-Acetyl-3-o-toluyl-5-fluorouracil are not detailed in the available literature. Given that the compound functions as a prodrug that requires metabolic activation to release the active 5-FU moiety, assays to evaluate its mechanism typically involve thymidylate synthase (TS) inhibition studies using purified enzyme preparations or cell-free systems, where the active metabolite’s ability to compete with deoxyuridine monophosphate (dUMP) for binding to TS can be quantified.
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| Cell Assay |
Cellular assays for evaluating the antiproliferative effects of 1-Acetyl-3-o-toluyl-5-fluorouracil can be performed using murine hepatoma cell lines or other 5-FU-sensitive tumor cells. Cells are seeded in appropriate culture medium at densities of 5 × 10³ cells/well in 96-well plates and cultured overnight. The test compound is dissolved in DMSO and diluted in culture medium to varying concentrations (typically 0.1-200 μM). Following 48-72 hours of incubation at 37°C in 5% CO₂, cell viability is assessed using MTT or CCK-8 assays, with IC50 values calculated from dose-response curves.
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| Animal Protocol |
A representative in vivo protocol using the murine hepatoma MH134 solid tumor model has been described . Tumor-bearing mice are divided into treatment and control groups. For oral administration, the compound is prepared as an oil solution and administered via stomach tube at doses of 0.2, 0.4, and 0.6 mmol/kg/day. For comparison, subcutaneous administration of 5-FU or A-OT-Fu is performed in the buttock region at the same dose levels. During the experimental period, body weight is measured every 3 days, and tumor dimensions (long and short diameters) are measured daily. Tumor growth inhibition is calculated, and organ weights (thymus, spleen) are recorded at study termination to evaluate immunotoxicity.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of 1-Acetyl-3-o-toluyl-5-fluorouracil have demonstrated that the compound exhibits favorable absorption and distribution characteristics following oral administration . In capsule formulation studies, A-OT-FU showed rapid oral absorption with an absorption half-life (t₁/₂ka) of 0.52 hours, rapid distribution (t₁/₂α) of 1.22 hours, and slow elimination (t₁/₂β) of 64.12 hours, enabling sustained maintenance of high blood drug concentrations . These properties indicate that the compound is well-suited for oral administration with once-daily or less frequent dosing regimens. The compound is typically stored as a solid powder at -20°C for long-term stability .
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| Toxicity/Toxicokinetics |
Preclinical toxicity evaluations of 1-Acetyl-3-o-toluyl-5-fluorouracil indicate a favorable safety profile compared to 5-FU . The level of decrease in thymus weight (indicating immunosuppression) and the magnitude of increase in spleen weight following oral administration of A-OT-Fu at any tested dose are smaller than those observed with subcutaneous 5-FU administration at 0.2 mmol/kg/day, suggesting reduced immunotoxicity . As a 5-FU analog, the compound may carry potential for similar adverse effects including gastrointestinal toxicity (diarrhea, stomatitis, nausea) and myelosuppression, though at reduced severity. The compound is strictly intended for research use only and is not approved for human therapeutic applications without appropriate authorization .
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| References |
[1]. Anti-tumor activity of 1-acetyl-3-o-toluyl-5-fluorouracil against murine hepatoma MH134 and its effects on tissue weights following subcutaneous and oral administration. J Pharmacobiodyn. 1985 Apr;8(4):264-9
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| Molecular Formula |
C14H11N2O4F
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|---|---|
| Molecular Weight |
290.24654
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| Exact Mass |
290.07
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| CAS # |
71861-76-2
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| PubChem CID |
126342
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.44g/cm3
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| Boiling Point |
408.8ºC at 760 mmHg
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| Flash Point |
201.1ºC
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| Index of Refraction |
1.609
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| LogP |
0.806
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
543
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C(C2=CC=CC=C2C)=O)C(C(F)=CN1C(C)=O)=O
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| InChi Key |
DRXHAKVGNKHFMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H11FN2O4/c1-8-5-3-4-6-10(8)12(19)17-13(20)11(15)7-16(9(2)18)14(17)21/h3-7H,1-2H3
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| Chemical Name |
1-acetyl-5-fluoro-3-(2-methylbenzoyl)pyrimidine-2,4-dione
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| Synonyms |
1-Acetyl-3,2-toluyl-5-fluorouracil; 1-acetyl-3-O-toluyl-5-fluorouracil; DTXSID00222129; 2,4(1H,3H)-Pyrimidinedione, 1-acetyl-5-fluoro-3-(2-methylbenzoyl)-;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.4453 mL | 17.2265 mL | 34.4531 mL | |
| 5 mM | 0.6891 mL | 3.4453 mL | 6.8906 mL | |
| 10 mM | 0.3445 mL | 1.7227 mL | 3.4453 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.
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