| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
E7766 diammonium salt specifically targets the STING protein, binding to it with a dissociation constant (Kd) of 40 nM as measured by isothermal titration calorimetry (ITC). It activates STING by stabilizing its dimeric conformation. This binding triggers the downstream TBK1/IRF3 signaling cascade, leading to the production of type I interferons (IFN-alpha/beta). It exhibits broad pan-genotypic activity in all major human STING variants.
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| ln Vitro |
Four human STING variants—human wild-type, HAQ, AQ, and REF STING proteins—are inhibited by E7766 diammonium salt, with corresponding EC50 values of 1.2 μM, 2.2 μM, 1.2 μM, and 4.9 μM [1].
In cell-free binding assays, E7766 diammonium salt demonstrates a Kd of 40 nM for STING, as determined by ITC, indicating high binding affinity. It shows potent pan-genotypic activity in all major human STING variants, including wild-type, HAQ, and R232H. E7766 has higher binding affinity than 2'3'-cGAMP, the natural STING ligand. In cellular assays using human THP-1 cells, E7766 potently induces IFN-beta production with EC50 values in the nanomolar range (approximately 1 microM across various STING genotypes). |
| ln Vivo |
A single intratumoral injection of 10 mg/kg E7766 diammonium salt was given into subcutaneous tumors in a mouse colon cancer model. In a mouse liver metastasis tumor model, E7766 diammonium salt exhibits strong anticancer activity and a long-lasting immunological memory response [1].
In vivo, E7766 diammonium salt displays potent anti-tumor activity in murine tumor models. Its macrocyclic bridge structure enhances metabolic stability, leading to sustained activation of the STING pathway. E7766 has been shown to induce durable anti-tumor immunity and tumor regression when administered intratumorally in established tumor models. The compound demonstrates pan-genotypic activity, making it effective across different STING genotypes. |
| Enzyme Assay |
The specific protocol for STING binding uses isothermal titration calorimetry (ITC). Recombinant human STING protein is dialyzed into ITC buffer. E7766 diammonium salt is dissolved in the same buffer. The STING protein is placed in the sample cell, and E7766 is titrated in 2-3 uL injections at 3-minute intervals. The heat change from each injection is measured and integrated. The binding curve is fit to a one-site binding model to calculate Kd (40 nM), binding stoichiometry (n), and thermodynamic parameters (deltaH, deltaS).
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| Cell Assay |
A standard in vitro cellular assay uses THP-1 human monocytic cells or primary human PBMCs isolated from donors with different STING genotypes (wild-type, HAQ, R232H, R293Q). Cells are seeded in 96-well plates and treated with a dilution series of E7766 diammonium salt (0.1 nM to 10 uM) for 6 hours. Total RNA is isolated and IFNB1 and CXCL10 mRNA levels are quantified by qRT-PCR. Cell culture supernatants are collected at 24 hours for IFN-beta ELISA measurement. EC50 values are calculated from concentration-response curves.
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| Animal Protocol |
An in vivo protocol for E7766 uses a MC38 syngeneic mouse colon carcinoma model. Female C57BL/6 mice are inoculated subcutaneously with 5×10⁵ MC38 cells. When tumors reach 50-100 mm3 (typically 7-10 days), mice receive intratumoral injections of E7766 diammonium salt (10-30 ug in 30 uL PBS) on days 7, 10, and 14. Tumor volumes are measured with calipers every 2-3 days. On day 21, tumors are excised and processed for flow cytometry to assess CD8+ T-cell infiltration, and spleens are collected for tetramer staining.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for E7766 diammonium salt is not publicly available. As a macrocycle-bridged cyclic dinucleotide analog, it is designed to have greater metabolic stability compared to unmodified cyclic dinucleotides, potentially leading to a longer half-life in vivo. For research applications, it is typically administered via intratumoral or intravenous routes to ensure adequate bioavailability at the target site. The diammonium salt formulation improves aqueous solubility.
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| Toxicity/Toxicokinetics |
Toxicology data for E7766 diammonium salt is limited to preclinical observations. As a STING agonist, the primary safety concern is immune-related adverse events, including cytokine release syndrome (CRS) and potential autoimmunity at high systemic doses. Standard safety assessment would include in vitro hERG inhibition testing, CYP450 enzyme inhibition screening, and a 14-day repeat-dose intratumoral toxicity study in rats to establish the maximum tolerated dose (MTD) and evaluate off-target effects.
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| References | |
| Additional Infomation |
E7766 diammonium salt is a research-grade chemical and is not approved for human therapeutic use. Its molecular formula is C20H21N10O12P2·2H3N, with a molecular weight of 780.66. The macrocycle-bridged structure distinguishes it from other STING agonists and contributes to its high binding affinity and pan-genotypic activity. It has higher binding affinity than 2‘3'-cGAMP and exhibits EC50 values of approximately 1 microM across human STING variants. This compound is stored at -20degC for long-term stability.
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| Molecular Formula |
C24H29F2N11O8P2S2
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|---|---|
| Molecular Weight |
763.63
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| Exact Mass |
746.081
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| CAS # |
2242635-03-4
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| Related CAS # |
E7766 disodium;2242636-28-6
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| PubChem CID |
163342335
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| Appearance |
White to off-white solid powder
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| LogP |
2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
48
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| Complexity |
1230
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| Defined Atom Stereocenter Count |
8
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| SMILES |
FC1([H])[C@@H]2O[P@@](OC[C@@]3([H])O[C@@]4([H])N5C=NC6C(=NC=NC5=6)NCC=CCN=C5N=CNC6=C5N=CN6[C@H]1O[C@]2([H])CO[P@@](O[C@@]3([H])[C@H]4F)(S)=O)(S)=O.N |c:26,t:29,&1:3,5,8,11,37,39,43,45,47|
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| InChi Key |
YQSAUMRQALUWNS-LFBLFPLGSA-N
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| InChi Code |
InChI=1S/C24H26F2N10O8P2S2/c25-13-17-11-5-39-46(38,48)44-18-12(6-40-45(37,47)43-17)42-24(14(18)26)36-10-34-16-20(30-8-32-22(16)36)28-4-2-1-3-27-19-15-21(31-7-29-19)35(9-33-15)23(13)41-11/h1-2,7-14,17-18,23-24H,3-6H2,(H,37,47)(H,38,48)(H,27,29,31)(H,28,30,32)/b2-1-/t11-,12-,13-,14-,17-,18-,23-,24-,45?,46?/m1/s1
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| Chemical Name |
(1R,3R,15Z,28R,29R,30R,31R,36R,41R)-29,41-difluoro-34,39-dihydroxy-34,39-bis(sulfanylidene)-2,33,35,38,40,42-hexaoxa-4,6,9,11,13,18,20,22,25,27-decaza-34λ5,39λ5-diphosphaoctacyclo[28.6.4.13,36.128,31.04,8.07,12.019,24.023,27]dotetraconta-5,7(12),8,10,15,19(24),20,22,25-nonaene
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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 and light. |
| 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: 45 mg/mL (57.64 mM)
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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 | 1.3095 mL | 6.5477 mL | 13.0953 mL | |
| 5 mM | 0.2619 mL | 1.3095 mL | 2.6191 mL | |
| 10 mM | 0.1310 mL | 0.6548 mL | 1.3095 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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