| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The compound targets dUTPase and DPD. dUTPase is an enzyme that prevents the incorporation of dUTP into DNA, protecting cancer cells from aberrant base-mediated cytotoxicity during thymidylate synthase inhibition. DPD is the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. By inhibiting DPD, TAS-114 prevents first-pass metabolism of 5-FU, allowing oral administration and increasing efficacy.
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| ln Vitro |
The cytotoxicity of 2-deoxy-5-fluorouridine (FdUrd) and 5-fluorouracil (5-FU) against various mold strains is enhanced in a dose-dependent manner by TAS-114 (1-10 μM; 72 hours) [1].
In vitro, TAS-114 enhances the cytotoxicity of 2-deoxy-5-fluorouridine (FdUrd) and 5-fluorouracil (5-FU) against various cancer cell lines in a dose-dependent manner at 1-10 μM for 72 hours. It enhances the antitumor activity of 5-FU by preventing the hydrolysis and breakdown of 5-fluoro-deoxyuridine triphosphate (FdUTP) and dUTP. |
| ln Vivo |
TAS-114 (37.5-1, 200 mg/kg/day; sidewall; days 1-14) enhances capecitabine (539 mg/kg/day) and 5-FU anti-tumor efficacy in mice.
In vivo, TAS-114 enhances capecitabine and 5-FU anti-tumor efficacy in mice at 37.5-1,200 mg/kg/day (oral, days 1-14). Co-administration with TAS-114 allows lower dosing of 5-FU prodrugs, which decreases 5-FU-related toxicity while maintaining therapeutic levels of 5-FU at the tumor site. It is an orally bioactive inhibitor. |
| Enzyme Assay |
In vitro enzyme assays for TAS-114 involve measuring dUTPase and DPD activities. Recombinant enzymes are incubated with substrates and varying concentrations of TAS-114. Enzyme activity is quantified by measuring substrate conversion or product formation. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Cytotoxicity assay[1]
Cell Types: HeLa, NUGC-4, NCI-H441, HT-29, CFPAC-1 and MCF-7 Cell line Tested Concentrations: 72 hrs (hours) Incubation Duration: 1 μM, 3 μM and 10 μM Experimental Results: The cytotoxicity of FdUrd and 5-FU to various cancer cell lines was Dramatically increased in a dose-dependent manner. For in vitro cell-based assays, cancer cell lines such as HeLa, NUGC-4, NCI-H441, HT-29, CFPAC-1, and MCF-7 are cultured and treated with TAS-114 (1, 3, and 10 μM) for 72 hours. Cytotoxicity of FdUrd and 5-FU is assessed using MTT or similar assays. |
| Animal Protocol |
Animal/Disease Models: BALB/c nude mouse MX-1 human breast cancer xenograft [1]
Doses: 37.5 to 1,200 mg/kg/day Route of Administration: Oral; active [1]. Routine; Days 1-14 Experimental Results: The tolerated dose of capecitabine (539 mg/kg/day) was diminished in mice in a dose-dependent manner. In vivo animal studies for TAS-114 use BALB/c nude mouse MX-1 human breast cancer xenograft models. TAS-114 is administered orally at 37.5 to 1,200 mg/kg/day for 14 days. Capecitabine (539 mg/kg/day) is co-administered. Anti-tumor efficacy is assessed by measuring tumor growth. |
| ADME/Pharmacokinetics |
TAS-114 (CAS 1198221-21-4) has a molecular formula of C21H29N3O6S and a molecular weight of 451.45. It is soluble in DMSO. It is an orally bioactive small molecule. Detailed pharmacokinetic parameters are not extensively characterized.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TAS-114 are not extensively provided. As a dUTPase and DPD inhibitor, it would be expected to have a safety profile related to nucleotide metabolism and fluoropyrimidine modulation. Co-administration allows lower dosing of 5-FU prodrugs, decreasing 5-FU-related toxicity.
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| References | |
| Additional Infomation |
TAS-114, a dUTPase/DPD inhibitor, is an orally bioavailable inhibitor of deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD) with potential adjuvant antitumor activity. When administered orally in combination with a prodrug of the pyrimidine antagonist 5-fluorouracil (5-FU), TAS-114 inhibits DPD (a hepatic enzyme responsible for the rapid degradation of 5-FU into inactive metabolites). This blocks the first-pass metabolism of 5-FU, allowing for the oral administration of the 5-FU prodrug and enhancing the efficacy of 5-FU. Furthermore, as a dUTPase inhibitor, TAS-114 enhances the antitumor activity of 5-FU by inhibiting the hydrolysis and degradation of its active metabolites, 5-fluorodeoxyuridine triphosphate (FdUTP) and deoxyuridine triphosphate (dUTP). This promotes the DNA polymerase-dependent incorporation of these antimetabolites into DNA, leading to DNA damage and tumor cell death. Combining with TAS-114 can reduce the dose of 5-FU prodrug, thereby reducing 5-FU-related toxicity, while maintaining the therapeutic concentration of 5-FU at the tumor site.
TAS-114 is a first-in-class oral dUTPase inhibitor. It is a dual-target inhibitor of dUTPase and DPD that enhances the efficacy of fluoropyrimidine-active molecules. It has potential antineoplastic adjuvant activity. No approved therapeutic status is reported. |
| Molecular Formula |
C21H29N3O6S
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| Molecular Weight |
451.536464452744
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| Exact Mass |
451.177
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| CAS # |
1198221-21-4
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| Related CAS # |
1198221-48-5 (Racemic);1198221-21-4 (R-isomer);
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| PubChem CID |
53630253
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| Appearance |
White to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
31
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| Complexity |
745
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(CCCOCN1C=CC(NC1=O)=O)(N[C@H](C)C1=CC=CC(=C1)OC1CCCC1)(=O)=O
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| InChi Key |
AMCGLRWKUQPNKD-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C21H29N3O6S/c1-16(17-6-4-9-19(14-17)30-18-7-2-3-8-18)23-31(27,28)13-5-12-29-15-24-11-10-20(25)22-21(24)26/h4,6,9-11,14,16,18,23H,2-3,5,7-8,12-13,15H2,1H3,(H,22,25,26)/t16-/m1/s1
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| Chemical Name |
N-[(1R)-1-(3-cyclopentyloxyphenyl)ethyl]-3-[(2,4-dioxopyrimidin-1-yl)methoxy]propane-1-sulfonamide
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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 (e.g. under nitrogen), 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) |
DMSO : ~100 mg/mL (~221.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2146 mL | 11.0732 mL | 22.1464 mL | |
| 5 mM | 0.4429 mL | 2.2146 mL | 4.4293 mL | |
| 10 mM | 0.2215 mL | 1.1073 mL | 2.2146 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02855125
Conditions:Advanced or Metastatic Non-small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT02454062
Conditions:Advanced Solid TumorsLink: https://clinicaltrials.gov/ct2/show/NCT01610479
Conditions:Advanced Solid TumorsProducts are for research use only; We do not sell to patients
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