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Purity: ≥98%
C-176 is a highly potent, covalent/irreversible and selective small-molecule antagonist/inhibitor of the stimulator of interferon genes (STING) protein, which is a central signalling component of the intracellular DNA sensing pathway. Mechanistically, C-176 covalently targets the predicted transmembrane cysteine residue 91 and thereby block the activation-induced palmitoylation of STING. The palmitoylation of STING is essential for its assembly into multimeric complexes at the Golgi apparatus and, in turn, for the recruitment of downstream signalling factors. C-176 and its derivatives reduce STING-mediated inflammatory cytokine production in both human and mouse cells. Furthermore, C-176 attenuates pathological features of autoinflammatory disease in mice. In summary, this work uncovers a mechanism by which STING can be inhibited pharmacologically and demonstrates the potential of therapies that target STING for the treatment of autoinflammatory disease.
| ln Vitro |
C-176 significantly inhibits IFNβ reporter activity mediated by STING, but not by RIG-I or TBK1. Type I IFN and IL-6 serum level induction mediated by CMA is significantly inhibited by pretreatment with C-176[1].
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| ln Vivo |
Without causing considerable toxicity, C-176 (750/375 nmol C-176 per mouse in 200 μL corn oil) greatly lowers the CMA-mediated activation of type I IFNs and IL-6 blood levels[1]. With no obvious symptoms of overt toxicity in Trex1−/− mice, C-176 significantly lowers serum levels of type I IFNs and strongly suppresses inflammatory markers in the heart[1]. In Trex1−/− mice, C-176 significantly reduces a number of indicators of systemic inflammation [
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| Animal Protocol |
Animal/Disease Models: WT type mice.
Doses: 750/375 nmol C-176 per mouse in 200 μL corn oil (~1.34/0.67 mg/mL). Route of Administration: Intraperitoneally, once. Experimental Results: Dramatically decreased Serum levels of type I IFNs and IL-6. |
| References |
[1]. Haag SM, et al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018 Jul;559(7713):269-273.
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| Molecular Formula |
C11H7IN2O4
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| Molecular Weight |
358.09
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| CAS # |
314054-00-7
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| Related CAS # |
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| SMILES |
O=C(C1=CC=C([N+]([O-])=O)O1)NC2=CC=C(I)C=C2
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.67 mg/mL (4.66 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 0.25 mg/mL (0.70 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 2.5 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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. View More
Solubility in Formulation 3: ≥ 0.25 mg/mL (0.70 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.25 mg/mL (0.70 mM) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 2.5 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. Solubility in Formulation 5: 10 mg/mL (27.93 mM) in Cremophor EL (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7926 mL | 13.9630 mL | 27.9259 mL | |
| 5 mM | 0.5585 mL | 2.7926 mL | 5.5852 mL | |
| 10 mM | 0.2793 mL | 1.3963 mL | 2.7926 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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