| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
TAK-676 (TAK676) is a novel STING agonist that is able to trigger the activation of STING signaling pathway and type I interferons. It is also a modulator of immune system, resulting complete regressions and durable memory T-cell immunity. TAK-676 can promote durable IFN-dependent antitumor immunity.
| ln Vitro |
In THP1-Dual human AML cells and CT26.WT cells, dazostinag disodium (1.1, 3.3, and 10 μM; 2 h) dose-dependently activates the STING-TBK1-IRF3 pathway, however it is significantly dependent on STING expression[1]. In vitro immune cell activation activity of disodium (0-1 μM; 24 h) on mouse BM-derived dendritic cells is dose-dependent[1]. Dendritic cells (DC), natural killer (NK) cells, and T cells are all activated more readily by dazostigman disodium (0-1 μM; 24 h); activation EC50s are 1.27 μM (MoDC), 0.32 μM (BMDC), 0.271 μM (NK), 0.216 μM (CD8+), and 0.249 μM (CD4+) at 24 h, respectively[1].
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| ln Vivo |
Dazostinag disodium (0.025–2 mg/kg; IV; single dose) is more exposed in mice's tumors, has dose-proportional pharmacokinetics in plasma, and is well tolerated[1]. BALB/c mice with A20 syngeneic tumors/CT26.WT syngeneic tumors mode demonstrate anti-tumor function when administered with dazostinag disodium (1 mg/kg/d, 2 mg/kg/d; iv; 13 d)[1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: THP1-Dual human AML cells and CT26.WT cells Tested Concentrations: 1.1, 3.3, 10 μM Incubation Duration: 2 hrs (hours) Experimental Results: Increased pTBK1, pSTING, pIRF3 protein level in a dose-dependent manner. Not induced the phosphorylation of pTBK1 (S172) or pIRF3 (S396) in the absence of STING expression. |
| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse bearing A20 syngeneic tumors/CT26. WT syngeneic tumors model[1]
Doses: 1 or 2 mg/kg/day Route of Administration: intravenous (iv) injection; for 3, 6, 9, 12 day, respectively Experimental Results: Resulted in significant T cell–dependent in vivo antitumor activity. Induced dose- dependent cytokine responses and increased the activation and proliferation of immune cells within the TME and tumor-associated lymphoid tissue. |
| References | |
| Additional Infomation |
Dazostinag Disodium is the disodium salt form of dazostinag, an agonist of the stimulator of interferon genes protein (STING; transmembrane protein 173; TMEM173), with potential immunoactivating and antineoplastic activities. Upon intravenous administration, dazostinag targets and binds to STING and activates the STING pathway in immune cells in the tumor microenvironment (TME). This leads to the production of pro-inflammatory cytokines, including interferons (IFNs), enhances the cross-presentation of tumor-associated antigens (TAAs) by dendritic cells (DCs), and induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. STING, a transmembrane protein that activates immune cells in the TME, plays a key role in the activation of the innate immune system.
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| Molecular Formula |
C21H20F2N8NA2O10P2S2
|
|---|---|
| Molecular Weight |
754.484971046448
|
| Exact Mass |
753.998
|
| CAS # |
2553413-93-5
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| Related CAS # |
Dazostinag;2553413-86-6
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| PubChem CID |
165412584
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
2
|
| Heavy Atom Count |
47
|
| Complexity |
1300
|
| Defined Atom Stereocenter Count |
8
|
| SMILES |
S=P1([O-])OC[C@@H]2[C@H]([C@H]([C@H](N3C=NC4C(N)=NC=NC3=4)O2)F)OP(=O)(OC[C@@H]2[C@H]([C@H]([C@H](N3C=C(C4C(NC=NC3=4)=O)F)O2)O1)O)[S-].[Na+].[Na+]
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| InChi Key |
DSMDURFDSXGNPW-RLKXMDTLSA-L
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| InChi Code |
InChI=1S/C21H22F2N8O10P2S2.2Na/c22-7-1-30(17-10(7)19(33)28-5-26-17)21-15-13(32)8(38-21)2-36-42(34,44)40-14-9(3-37-43(35,45)41-15)39-20(11(14)23)31-6-29-12-16(24)25-4-27-18(12)31;;/h1,4-6,8-9,11,13-15,20-21,32H,2-3H2,(H,34,44)(H,35,45)(H2,24,25,27)(H,26,28,33);;/q;2*+1/p-2/t8-,9-,11-,13-,14-,15-,20-,21-,42?,43?;;/m1../s1
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| Chemical Name |
disodium;7-[(1R,6R,8R,9R,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9-fluoro-18-hydroxy-12-oxido-3-oxo-12-sulfanylidene-3-sulfido-2,4,7,11,13,16-hexaoxa-3λ5,12λ5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-5-fluoro-3H-pyrrolo[2,3-d]pyrimidin-4-one
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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 | 1.3254 mL | 6.6270 mL | 13.2540 mL | |
| 5 mM | 0.2651 mL | 1.3254 mL | 2.6508 mL | |
| 10 mM | 0.1325 mL | 0.6627 mL | 1.3254 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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