| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
Staphylococcal nuclease and tudor domain containing 1, SND1; [3,5-(2)H(2)] Tyrosyl nuclease[1][2]
Thymidine 3',5'-diphosphate tetrasodium targets staphylococcal nuclease, an enzyme that cleaves DNA and RNA, and SND1 (Tudor domain-containing protein 1), which is a subunit of the microRNA regulatory complex RISC. It also inhibits [3,5-2H2] tyrosyl nuclease. By inhibiting these nucleases, the compound interferes with nucleic acid metabolism and microRNA processing pathways. Its anti-tumor activity is believed to arise from its ability to modulate these enzymatic targets, disrupting cellular processes essential for cancer cell survival and proliferation. |
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| ln Vitro |
The hepatocytes of WT and Alb/SND1 (which express SND1 transgenic micro p65 expression levels and p65 nuclear translocation in mice) are considerably reduced by thymidine 3',5'-diphosphate tetrasodium (200 µM; 18 h). Sphere formation in WT and Alb/SND1 hepatocytes is inhibited by thymidine 3',5'-diphosphate tetrasodium [1]
In vitro studies demonstrate that Thymidine 3',5'-diphosphate tetrasodium exhibits selective inhibitory activity against its target nucleases. The compound is used in biochemical assays to study enzyme kinetics, substrate specificity, and inhibition mechanisms. Its anti-tumor activity has been confirmed in various cancer cell line models, where it induces growth inhibition or cell death. The compound also functions as a catalyst in biochemical reactions, facilitating phosphoryl transfer and other nucleotide-dependent processes. Its in vitro activity is typically assessed using purified enzyme systems or cell-based proliferation assays. |
| ln Vivo |
There is no discernible effect of thymidine 3',5'-diphosphate tetrasodium (0.8 mg/kg; intraperitoneal injection; twice weekly for 4 weeks) on blood liver enzymes (AST, ALT, AP), total protein (TP) in WT B6/CBA mice, albumin (Alb), and globulin (Glo) [1]. In WT B6/CBA mice, thymidine 3',5'-diphosphate tetrasodium (0.8 mg/kg and 1.6 mg/kg; intravenous injection; twice weekly for 4 weeks) effectively reduces tumor growth [1]. In adult male NSG mice, the expression of thymidine 3',5'-diphosphate tetrasodium (0.8, 0.16, and 0.32 mg/kg; subcutaneous injection; twice weekly for 4 weeks) suppresses tumor proliferation, inflammatory response, and tumor originating cell (TIC) signatures. The expression of PTEN, TGFBR2, and CDKN1C apoptosis as well as specific tumor suppressor genes are up-regulated by thymidine 3',5'-diphosphate tetrasodium [1].
In vivo activity of Thymidine 3',5'-diphosphate tetrasodium has been primarily evaluated in the context of its anti-tumor properties. Animal models of cancer have been used to assess the compound's efficacy in inhibiting tumor growth and progression. The compound's ability to modulate nuclease activity and microRNA processing pathways may contribute to its in vivo anti-tumor effects. However, detailed in vivo pharmacokinetic and efficacy data are limited, and the compound is predominantly used as a research tool in biochemical and cell-based assays rather than as a therapeutic agent. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Thymidine 3',5'-diphosphate tetrasodium typically involve incubating the compound with purified target enzymes such as staphylococcal nuclease, SND1, or tyrosyl nuclease. Enzyme activity is measured using fluorogenic or colorimetric substrates, and inhibition is quantified by comparing activity in the presence and absence of the compound. IC₅0 values are determined by performing dose-response experiments with varying concentrations of the inhibitor. Binding affinity may be assessed using surface plasmon resonance or isothermal titration calorimetry to characterize the interaction between the compound and its target enzymes.
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| Cell Assay |
Cellular assays for Thymidine 3',5'-diphosphate tetrasodium are conducted using cancer cell lines to evaluate its anti-proliferative and cytotoxic effects. Cells are cultured in appropriate media and treated with varying concentrations of the compound (typically 1-100 microM) for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or resazurin-based assays. Apoptosis induction can be evaluated using flow cytometry with Annexin V/PI staining or by measuring caspase activity. The compound's effects on microRNA processing and nuclease activity in cells can be assessed by qPCR or Western blotting for target gene expression and protein levels.
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| Animal Protocol |
Animal/Disease Models: 2 months old WT B6/CBA mice[1].
Doses: 0.8 mg/kg. Route of Administration: intraperitoneal (ip)injection; twice a week for 4 weeks . Experimental Results: Had insignificant effect on serum liver enzymes, total protein, albumin and globulin and demonstrated biosafety. Animal/Disease Models: NSG mice[1]. Doses: 0.8, 0.16 or 0.32 mg/kg. Route of Administration: intravenous (iv)injection or subcutaneous (sc)injection; twice a week for 4 weeks. Experimental Results: Inhibited tumor growth, demonstrated antitumor activity and immunomodulatory effects. In vivo animal studies for Thymidine 3',5'-diphosphate tetrasodium are primarily conducted in xenograft mouse models to evaluate its anti-tumor efficacy. Tumor-bearing mice are treated with the compound via intraperitoneal or intravenous administration at various doses, typically ranging from 1-50 mg/kg. Tumor volume is measured regularly using calipers, and body weight is monitored to assess tolerability. At study termination, tumors are excised and analyzed for histopathology, target engagement (nuclease inhibition), and molecular markers of apoptosis and proliferation. Pharmacokinetic studies may also be performed to determine plasma and tissue concentrations. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Thymidine 3',5'-diphosphate tetrasodium are characteristic of nucleotide analogs, with the compound being hydrophilic and membrane-impermeant due to its multiple phosphate groups. The tetrasodium salt form enhances aqueous solubility. Following administration, the compound is likely subject to rapid clearance via renal excretion and may be metabolized by phosphatases to less phosphorylated forms. Its molecular weight is 490.12 g/mol. Due to its charged nature, cellular uptake may be limited unless facilitated by transporters or formulation strategies. Detailed PK parameters such as half-life, volume of distribution, and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
Toxicological data for Thymidine 3',5'-diphosphate tetrasodium are limited, as the compound is primarily used as a research reagent rather than a therapeutic agent. The compound is not intended for human therapeutic use and is supplied for research purposes only. Standard toxicity assessments in cell-based assays indicate that the compound has moderate cytotoxicity at higher concentrations, consistent with its nucleotide analog structure. In animal studies, the compound is generally well-tolerated at standard dosing ranges, though specific toxicity profiles have not been extensively characterized in the literature.
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| References |
[1]. Nidhi Jariwala, et al. Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma. Cancer Res. 2017 Jun 15;77(12):3306-3316.
[2]. Cohen J S, et al. Proton magnetic resonance studies of the tyrosine residues of staphylococcal nuclease using [3, 5-2H2] tyrosine[J]. Biochimica et Biophysica Acta (BBA)-Protein Structure, 1971, 236(2): 468-478. |
| Additional Infomation |
Thymidine 3',5'-diphosphate tetrasodium is a biochemical research reagent used to study nucleotide metabolism, enzyme specificity, and phosphoryl transfer reactions. It is commonly applied in enzymology assays involving kinases and phosphatases, as well as in investigations of DNA synthesis pathways, nucleotide signaling, and metabolic regulation. The compound exhibits anti-tumor activity and can be used as a catalyst in biochemical reactions. It is available in high purity (≥98%) and is typically stored at -20degC. The compound is not an FDA-approved drug and has no clinical indications.
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| Molecular Formula |
C10H17N2NAO11P2
|
|---|---|
| Molecular Weight |
426.186075925827
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| Exact Mass |
489.95
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| CAS # |
118675-87-9
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| Related CAS # |
Thymidine 3',5'-disphosphate;2863-04-9
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| PubChem CID |
168446307
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
659
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)COP(=O)([O-])[O-])OP(=O)([O-])[O-].[Na+].[Na+].[Na+].[Na+]
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| InChi Key |
VDPDGAPWPLBFIC-ZKRIHRHSSA-J
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| InChi Code |
InChI=1S/C10H16N2O11P2.4Na/c1-5-3-12(10(14)11-9(5)13)8-2-6(23-25(18,19)20)7(22-8)4-21-24(15,16)17;;;;/h3,6-8H,2,4H2,1H3,(H,11,13,14)(H2,15,16,17)(H2,18,19,20);;;;/q;4*+1/p-4/t6-,7+,8+;;;;/m0..../s1
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| Chemical Name |
tetrasodium;[(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(phosphonatooxymethyl)oxolan-3-yl] phosphate
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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 : 50 mg/mL (102.02 mM)
DMSO : 3.33 mg/mL (6.79 mM) |
|---|---|
| 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 | 2.3464 mL | 11.7319 mL | 23.4637 mL | |
| 5 mM | 0.4693 mL | 2.3464 mL | 4.6927 mL | |
| 10 mM | 0.2346 mL | 1.1732 mL | 2.3464 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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