E7766 (E-7766) is a macrocycle-bridged STING (Stimulator of Interferon Genes) agonist (Kd = 40 nM) with antitumor activities.

Physicochemical Properties

Molecular Formula	C24H26F2N10O8P2S2
Molecular Weight	746.5983
Exact Mass	746.082
CAS #	2242635-02-3
Related CAS #	2242635-03-4 (diammonium salt); 2242636-28-6 (disodium salt)
PubChem CID	153278332
Appearance	Typically exists as solid at room temperature
Density	2.15±0.1 g/cm3(
LogP	1.2
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	20
Rotatable Bond Count	0
Heavy Atom Count	48
Complexity	1330
Defined Atom Stereocenter Count	8
SMILES	SP1(=O)OC[C@@H]2[C@@H]3[C@H]([C@H](N4C=NC5C(=NC=NC4=5)NCC=CCNC4=C5C(=NC=N4)N(C=N5)[C@H]4[C@@H]([C@@H]([C@@H](COP(O)(O3)=S)O4)O1)F)O2)F |c:22|
InChi Key	YQSAUMRQALUWNS-VUCARUFASA-N
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
Chemical Name	(19S,22R,23R,23aR,25R,27aR,29R,210R,210aR,212S,214aR,39S,E)-23,210-difluoro-25,212-dimercapto-23,23a,27a,29,210,210a,214,214a-octahydro-19H,22H,27H,39H-4,9-diaza-1,3(9,6)-dipurina-2(2,9)-difuro[3,2-d
Synonyms	E-7766 E 7766 E7766
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
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

ln Vitro	E7766 disodium inhibits four human STING variants, human wild-type, HAQ, AQ and REF STING proteins, with EC50 values of 1 μM, 2.2 μM, 1.2 μM and 4.9 μM, respectively[1].
ln Vivo	In murine colon cancer model, a single intratumoral injection of 10 mg/kg E7766 disodium in the subcutaneous tumor. E7766 disodium is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model[1].
References	:E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity. ChemMedChem. 2021 Jun 7;16(11):1740-1743.
Additional Infomation	Macrocycle-bridged STING Agonist E7766 is an agonist of macrocycle-bridged stimulator of interferon genes (STING) protein, with potential immunoactivating and antineoplastic activities. Upon intravenous administration, macrocycle-bridged STING agonist (MBSA) E7766 targets and binds to STING and activates the STING pathway, which promotes IKK-related kinase TANK-binding kinase 1 (TBK1) signaling and activates nuclear factor-kappa B (NF-kB) and interferon regulatory factor 3 (IRF3) in immune cells in the tumor microenvironment (TME). This leads to the production of pro-inflammatory cytokines, including interferons (IFNs). Specifically, expression of IFN-beta (IFNb) enhances the cross-presentation of tumor-associated antigens (TAAs) by CD8alpha-positive and CD103-positive dendritic cells (DCs) to cytotoxic T-lymphocytes (CTLs). This results in a CTL-mediated immune response against tumor cells and causes tumor cell lysis. Compared to conventional STING agonists, MBSA E7766 allows for conformational rigidity of the unique macrocycle bridge which enhances its stability and STING affinity, thereby increasing its efficacy.

Solubility Data

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

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	1.3394 mL	6.6970 mL	13.3941 mL
	5 mM	0.2679 mL	1.3394 mL	2.6788 mL
	10 mM	0.1339 mL	0.6697 mL	1.3394 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.