| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
STING-IN-6 targets the STING protein, acting as a direct antagonist that prevents its activation. By inhibiting STING, it blocks downstream signaling events including phosphorylation of TBK1 and IRF3, thereby preventing the transcription of type I interferon genes (IFN-beta and ISGs). This compound is a potent STING inhibitor (antagonist) with a pIC50 of 8.9, indicating its significant inhibitory capacity.
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| ln Vitro |
In cell-free biochemical assays, STING-IN-6 (compound 50) is a potent STING inhibitor (antagonist) with a pIC50 of 8.9, which corresponds to an IC50 of approximately 1.3 nM. This indicates extremely high binding affinity for the STING protein. The compound inhibits cGAMP-induced IFNbeta production in PBMCs with an IC50 of 49 nM, confirming its activity in a cellular context and its ability to block the canonical STING signaling pathway.
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| ln Vivo |
Specific in vivo activity data for STING-IN-6 has not been published. As a potent STING inhibitor, it may be utilized in immunological research to study the role of STING in autoimmune diseases. Inhibition of the STING pathway could potentially reduce type I interferon production and ameliorate disease symptoms in animal models of conditions such as Aicardi-Goutières syndrome, lupus, and other interferonopathies.
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| Enzyme Assay |
The specific protocol for STING binding inhibition uses a HTRF (homogeneous time-resolved fluorescence) competition binding assay. Recombinant human STING protein (wild-type) is incubated with a fluorescently-labeled STING agonist probe. A serial dilution of STING-IN-6 (0.01 nM to 10 uM) is added to the mixture. After a 2-hour equilibration at 25degC, the TR-FRET signal (emission ratio 665 nm/620 nm) is measured on a plate reader. The pIC50 value of 8.9 is calculated by fitting the inhibition curve using a 4-parameter logistic model.
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| Cell Assay |
For in vitro cellular assays, human PBMCs (peripheral blood mononuclear cells) are isolated from healthy donors via Ficoll-Paque density gradient centrifugation. PBMCs are seeded in 96-well plates at 2×10⁵ cells/well. Cells are pre-incubated with STING-IN-6 at concentrations ranging from 0.1 nM to 10 uM for 1 hour, then stimulated with 2‘3'-cGAMP (5 ug/mL) for 18 hours. Cell culture supernatants are collected, and human IFN-beta is quantified by ELISA. Alternatively, total RNA is extracted for qRT-PCR analysis of IFNB1 and CXCL10 expression. The IC50 for inhibition is calculated.
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| Animal Protocol |
An in vivo protocol for a STING inhibitor would involve a mouse model of STING-dependent autoimmunity. Female 6-8 week old Trex1 knockout mice (which exhibit STING-dependent autoinflammatory disease) are administered STING-IN-6 daily via intraperitoneal injection (1-20 mg/kg in formulation). After 4 weeks of treatment, mice are euthanized. Serum is collected for IFN-beta ELISA, and heart tissue is harvested for histopathological assessment of inflammatory infiltrates (a key pathology in Trex1-/- mice). Clinical scores (weight loss, skin lesions) are monitored throughout the study.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for STING-IN-6 has not been published. As a small molecule STING inhibitor, a standard PK study in C57BL/6 mice would involve IV (1 mg/kg) and PO (10 mg/kg) administration. Serial plasma samples would be collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose. STING-IN-6 concentrations would be quantified by LC-MS/MS. Key parameters including T1/2, Cmax, AUC, and oral bioavailability would be determined using non-compartmental analysis.
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| Toxicity/Toxicokinetics |
Toxicology data for STING-IN-6 is not available in standard databases. As a STING inhibitor, the primary safety concern would be increased susceptibility to infections due to suppression of type I interferon responses, which are critical for antiviral immunity. Standard safety assessment would include in vitro hERG channel inhibition testing, CYP450 enzyme inhibition screening, and a 14-day repeat-dose toxicity study in rats to establish the maximum tolerated dose (MTD).
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| References | |
| Additional Infomation |
STING-IN-6 is a research-grade compound and is not approved for clinical use. Its molecular formula is C46H52N12O6 with a molecular weight of 868.98. It is a potent STING inhibitor (antagonist) with pIC50 of 8.9. STING-IN-6 inhibits cGAMP-induced IFNbeta in PBMCs with IC50 of 49 nM. This compound may be utilized in immunological research. It is stored at -20degC for long-term stability and is soluble in DMSO.
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| Molecular Formula |
C46H52N12O6
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|---|---|
| Molecular Weight |
868.981888771057
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| Exact Mass |
868.413
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| CAS # |
2305940-34-3
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| PubChem CID |
138523782
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| Appearance |
White to off-white solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
64
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| Complexity |
1830
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=N/C(C2N(CC)N=C(C)C=2)=O)\N(C/C(/C)=C(\C)/CN2/C(=N/C(C3N(CC)N=C(C)C=3)=O)/N(C)C3=CC(C(N)=O)=CC=C32)C2=C(OCC3=CC=CC(OC)=C3)C=C(C(N)=O)C=C2N\1C
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| InChi Key |
DPZRWCJECJWXRN-LDNMNVMYSA-N
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| InChi Code |
InChI=1S/C46H52N12O6/c1-10-57-37(17-28(5)51-57)43(61)49-45-53(7)35-20-31(41(47)59)15-16-34(35)55(45)23-26(3)27(4)24-56-40-36(54(8)46(56)50-44(62)38-18-29(6)52-58(38)11-2)21-32(42(48)60)22-39(40)64-25-30-13-12-14-33(19-30)63-9/h12-22H,10-11,23-25H2,1-9H3,(H2,47,59)(H2,48,60)/b27-26+,49-45?,50-46?
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| Chemical Name |
1-[(E)-4-[5-carbamoyl-2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-3-methylbenzimidazol-1-yl]-2,3-dimethylbut-2-enyl]-2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-7-[(3-methoxyphenyl)methoxy]-3-methylbenzimidazole-5-carboxamide
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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) |
DMSO: ~100 mg/mL (~115.1 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.88 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (2.88 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1508 mL | 5.7539 mL | 11.5077 mL | |
| 5 mM | 0.2302 mL | 1.1508 mL | 2.3015 mL | |
| 10 mM | 0.1151 mL | 0.5754 mL | 1.1508 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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