Thymidine 3',5'-diphosphate (Deoxythymidine 3',5'-diphosphate) tetrasodium is a staphylococcal nuclease and a Tudor domain-containing 1 (SND1, RISC subunit of the MicroRNA regulatory complex) with [3,5-2H2 ] Selective inhibitor of tyrosyl nuclease ([3,5-2H2] tyrosyl nuclease). Thymidine 3',5'-diphosphate tetrasodium has anti-tumor activity and can also be used as a catalyst in biochemical reactions.

Physicochemical Properties

Molecular Formula	C10H17N2NAO11P2
Molecular Weight	426.186075925827
Exact Mass	489.95
CAS #	118675-87-9
Related CAS #	Thymidine 3',5'-disphosphate;2863-04-9
PubChem CID	168446307
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	29
Complexity	659
Defined Atom Stereocenter Count	3
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+]
InChi Key	VDPDGAPWPLBFIC-ZKRIHRHSSA-J
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
Chemical Name	tetrasodium;[(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(phosphonatooxymethyl)oxolan-3-yl] phosphate
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	Staphylococcal nuclease and tudor domain containing 1, SND1; [3,5-(2)H(2)] Tyrosyl nuclease[1][2]
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]
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].
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.
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.

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.