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Purity: ≥98%
| Targets |
Troxacitabine targets DNA polymerases, acting as a DNA chain terminator. As a nucleoside analog, troxacitabine is incorporated into DNA during replication, where it terminates DNA chain elongation by preventing the addition of subsequent nucleotides. This leads to the accumulation of DNA strand breaks and ultimately triggers apoptosis in rapidly dividing cancer cells. The compound's unnatural L-configuration and unique 1,3-dioxolane sugar ring contribute to its resistance to CDA-mediated degradation and its ability to enter cells via passive diffusion.
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| ln Vitro |
Hepatocellular carcinoma (HepG2), prostate (PC3, DUI45), non-small cell lung cancer (NCI-H460, NCr-322M), colon (HT29), and renal cancer (CAK-1, A498, RXF-) cell lines have demonstrated cytotoxicity when treated with trisatabine. With an IC50 range of 15-35 μM, they are of pancreatic origin (Pnac-Ol, MiaPa Ca) and 393 SNI2-C.
In vitro, troxacitabine has shown cytotoxicity in various cancer cell lines, including hepatocellular carcinoma (HepG2) and other solid tumor and hematological malignancy cell lines. Its potent anticancer activity is attributed to its ability to be incorporated into DNA and terminate chain elongation. The compound's unnatural L-configuration allows it to bypass nucleoside transporter-dependent uptake and resist degradation by CDA, enhancing its cellular accumulation and cytotoxic effects compared to conventional nucleoside analogs. |
| ln Vivo |
In the Panc-01 model, troxacitabine had substantial activity, as seen by TGI levels of 88.5% and 84.3% at doses of 10 mg/kg and 25 mg/kg, respectively. When comparing the mean final tumor weight of mice treated with troxacitabine to vehicle controls, this difference was statistically significant. Trisatabine's efficacy against the MiaPaCa model is minimal [3]. In human RCC tumor xenograft models, such as CAM-i, A498, RXF-393, and SN12C carcinomas, tresatabine exhibits remarkable efficacy. Animals with CAM-i, A498 and RXF-393 RCC tumors showed excellent responses when doses of 10, 25, and 50 mg/kg were administered intraperitoneally twice a day for five days [2].
In vivo, troxacitabine has been studied in animal models of cancer, demonstrating antitumor activity in various xenograft models. The compound's resistance to CDA degradation and ability to enter cells via passive diffusion contribute to its favorable in vivo efficacy. Troxacitabine has been evaluated in clinical trials for the treatment of solid tumors and hematological malignancies, but its development has been limited by toxicity concerns. The compound represents a unique approach to nucleoside analog therapy with potential advantages over conventional agents. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assays for troxacitabine are not typically performed because the compound's mechanism of action involves incorporation into DNA rather than binding to enzymes or receptors. However, the compound's ability to inhibit DNA polymerase activity can be assessed using cell-free DNA polymerase assays. In these assays, the incorporation of troxacitabine triphosphate into a DNA template by DNA polymerase is measured, and the extent of chain termination is evaluated. These assays confirm the compound's mechanism of action as a DNA chain terminator.
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| Cell Assay |
In vitro cellular assays for troxacitabine are performed using cancer cell lines. Cells are treated with varying concentrations of troxacitabine, and cell viability is measured using standard assays such as MTT or CellTiter-Glo. The IC50 for inhibition of cell proliferation is determined. Additionally, the compound's effects on cell cycle progression and apoptosis are assessed using flow cytometry. DNA strand break accumulation and incorporation of the compound into DNA can also be measured using specialized assays. These studies confirm the cytotoxic activity of troxacitabine in cancer cells.
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| Animal Protocol |
In vivo animal experiments for troxacitabine are conducted in mouse xenograft models of human cancers. Immunocompromised mice are implanted with human tumor cell lines (e.g., hepatocellular carcinoma, vulvar carcinoma, or breast carcinoma), and troxacitabine is administered via intraperitoneal or intravenous injection. Tumor growth inhibition is monitored, and endpoints include tumor volume, tumor weight, and survival. Pharmacodynamic markers such as DNA damage and apoptosis in tumor tissues are also assessed.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of troxacitabine are influenced by its unnatural L-configuration, which confers resistance to CDA-mediated degradation and allows it to bypass nucleoside transporter-dependent uptake. The compound has a molecular weight of 213.19 g/mol and a molecular formula of C8H11N3O4. Its unique structure contributes to a longer half-life and better oral bioavailability compared to conventional nucleoside analogs. Detailed pharmacokinetic parameters such as Cmax, AUC, and half-life have been characterized in preclinical and clinical studies.
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| Toxicity/Toxicokinetics |
Troxacitabine has been associated with dose-limiting toxicities in clinical studies, including myelosuppression, gastrointestinal toxicity, and hepatotoxicity. These adverse effects are consistent with the mechanism of action of nucleoside analogs, which target rapidly dividing cells, including bone marrow progenitor cells and gastrointestinal epithelial cells. The compound's development has been limited by these toxicity concerns. Preclinical toxicology studies have characterized the compound's safety profile, but further optimization may be needed to improve its therapeutic index.
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| References |
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| Additional Infomation |
Traxacitabine is a nucleobase-containing molecular entity and a carbohydrate derivative. Traxacitabine is a nucleoside analog with antitumor activity. There is increasing interest in its development for the treatment of patients with refractory lymphoproliferative disorders. Traxacitabine is a dioxolane derivative and a novel L-configuration deoxycytidine analog with potent antitumor activity. When tramaxacitabine is incorporated into the growing DNA strand during replication, it inhibits DNA polymerization due to its non-natural L-configuration (opposite to the normal D-configuration of nucleotides). Therefore, the drug terminates DNA synthesis upon incorporation into the DNA molecule, thereby inhibiting tumor cell proliferation. Drug Indications It has been studied for the treatment of myeloid leukemia. Mechanism of Action Traxacitabine is incorporated into DNA after activation by cellular kinases, inhibiting its replication. Unlike other cytosine nucleoside analogs, tramaxacitabine is not readily inactivated by cytidine deaminase (CD).
Pharmacodynamics Tresaxcitabine is a β-L-nucleoside analog that has shown preclinical antitumor activity in human xenograft tumor models and antileukemic responses in patients with relapsed myeloid leukemia. Troxacitabine is a nucleoside analog with potent anticancer activity, characterized by its unnatural L-configuration and unique 1,3-dioxolane sugar ring. It enters cells via passive diffusion, independent of nucleoside transporters, and is resistant to CDA-mediated degradation. Troxacitabine acts as a DNA chain terminator, leading to DNA strand breaks and apoptosis in cancer cells. The compound has been studied in clinical trials for the treatment of solid tumors and hematological malignancies but is not an approved drug. Its development highlights the potential of L-nucleoside analogs as anticancer agents. |
| Molecular Formula |
C8H11N3O4
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|---|---|
| Molecular Weight |
213.19064
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| Exact Mass |
213.075
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| CAS # |
145918-75-8
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| PubChem CID |
454194
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| Appearance |
White to off-white solid powder
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| Density |
1.71g/cm3
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| Boiling Point |
422.5ºC at 760mmHg
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| Flash Point |
209.3ºC
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| Vapour Pressure |
6.59E-09mmHg at 25°C
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| Index of Refraction |
1.694
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| LogP |
-1.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
328
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@H](O[C@H](O1)CO)N2C=CC(=NC2=O)N
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| InChi Key |
RXRGZNYSEHTMHC-MLWJPKLSSA-N
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| InChi Code |
InChI=1S/C8H11N3O4/c9-5-1-2-11(8(13)10-5)6-4-14-7(3-12)15-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6?,7-/m0/s1
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| Chemical Name |
4-amino-1-[(2S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]pyrimidin-2-one.
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| Synonyms |
BCH-4556; SGX-145; SPD-758; beta-L-OddC; BCH4556; SGX145; SPD758; brand name Troxatyl.
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 4.6907 mL | 23.4533 mL | 46.9065 mL | |
| 5 mM | 0.9381 mL | 4.6907 mL | 9.3813 mL | |
| 10 mM | 0.4691 mL | 2.3453 mL | 4.6907 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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