STING-IN-21
STING-IN-21 is an orally active and selective STING inhibitor with IC50 values of 33.0 nM and 43.8 nM for human and mouse STING, respectively. STING-IN-21 blocks the palmitoylation of STING, thereby inhibiting the translocation of STING to downstream compartments and the phosphorylation activation of downstream signaling pathways (such as TBK1, IRF3, NF-κB, etc.), ultimately downregulating the expression of pro-inflammatory cytokines and type I interferons. STING-IN-21 can be used for research on STING-mediated inflammatory diseases and autoimmune diseases (such as acute kidney injury and systemic lupus erythematosus).
For research use only. We do not sell to patients.
- CAS No.: 3105133-93-2
- Formula: C24H22F4N6O2
- Molecular Weight:502.46
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
hSTING 33.0 nM (IC50) |
mSTING 43.8 nM (IC50) |
NF-κB |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| THP1-Dual | IC50 |
33.0 nM
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Inhibition of human STING in THP1-Dual cells assessed by 2′,3′-cGAMP-induced luciferase reporter activity after overnight incubation.
Inhibition of human STING in THP1-Dual cells assessed by 2′,3′-cGAMP-induced luciferase reporter activity after overnight incubation.
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acs.jmedchem.6c02289 |
In Vitro
STING-IN-21 (1 μM; 2 h) blocks 2′,3′-cGAMP-induced STING palmitoylation in THP-1 cells[1].
STING-IN-21 (37) (100-500 nM; 1 h) inhibits 2',3'-cGAMP-induced STING/TBK1/IRF3 phosphorylation in THP-1 cells, as well as STING/TBK1/IRF3/P65 phosphorylation in L929 cells, and dose-dependently reverses the upregulated expression of downstream genes (IFNB, IL6, CXCL10, ISG15)[1].
STING-IN-21 (100 nM-1 μM; 4 h) shows no significant inhibitory effect on TLR3/4 signaling pathway (such as IFNB, CXCL10, IL6 expression) induced by LPS (HY-D1056) or poly (I:C) (HY-107202) stimulation in THP-1 cells, demonstrating its selectivity for the STING target[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1 and L929 cells
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Concentration:100 and 500 nM (STING-IN-21); 1 μg/mL (2′,3′-cGAMP)
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Incubation Time:1 h preincubation; 3 h stimulation (2′,3′-cGAMP)
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Result:In THP-1 cells, significantly inhibited phosphorylation of STING, TBK1, and IRF3, but not p65.
In L929 cells, significantly decreased phosphorylation of STING, TBK1, IRF3, and p65.
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Cell Line:THP-1 and L929 cells
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Concentration:100 and 500 nM (STING-IN-21); 1 μg/mL (2′,3′-cGAMP)
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Incubation Time:1 h preincubation; 3 h stimulation (2′,3′-cGAMP)
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Result:Dose-dependently reversed 2′,3′-cGAMP-induced upregulation of IFNB, IL6, CXCL10, and ISG15 in THP-1 cells and Ifnb, Il6, Cxcl10, and Isg15 in L929 cells.
In a wash-out experiment in L929 cells, retained potent inhibitory activity against STING downstream gene expression after washout.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | Bioavailability | Clearance (CL) | Vss |
|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 5 mg/kg | i.v. | 2.0 h | / | / | 3314 ng·h/mL | / | 25.2 mL/min/kg | 2.95 L/kg |
| Rat[1] | 20 mg/kg | p.o. | 2.3 h | 4.0 h | 483 ng/mL | 3256 ng·h/mL | 24.8 % | / | / |
| Mice[1] | 5 mg/kg | i.v. | 3.8 h | / | / | 7588 ng·h/mL | / | 11.1 mL/min/kg | 1.93 L/kg |
| Mice[1] | 20 mg/kg | p.o. | 2.7 h | 0.5 h | 1980 ng/mL | 6497 ng·h/mL | 21.4 % | / | / |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (female, 8-10 weeks old)[1]
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Dosage:10, 30 mg/kg
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Administration:p.o.; single dose; 2 h before CMA challenge
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Result:Dose-dependently reversed CMA-induced elevations in serum IFN-α, IFN-β, and IL-6 at 10 and 30 mg/kg.
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Animal Model:Trex1−/− (Strain T013987, 6 weeks old)[1]
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Dosage:30 mg/kg
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Administration:p.o.; once daily; 2 weeks
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Result:Decreased serum IFN-α, IFN-β, and IL-6 at 30 mg/kg.
Also reduced mRNA expression of Cxcl10, Isg15, Ccl2, Ifit1, Ifit3, Ifi44, and Irf7 in lung, liver, skeletal muscle, and kidney.
Attenuated multiorgan inflammation in lung, liver, muscle, and kidney.
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Animal Model:C57BL/6J (male, 10 weeks old)[1]
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Dosage:3, 10, 30 mg/kg
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Administration:p.o.; once daily; for 4 consecutive days
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Result:Slightly slowed cisplatin-induced body-weight loss at 30 mg/kg.
No mortality occurred in the 30 mg/kg group, whereas two mice died in the cisplatin-only group.
Dose-dependently reduced cisplatin-induced elevations in serum CREA and BUN.
Alleviated tubular dilation, necrosis, interstitial edema, and proteinaceous casts.
Dose-dependently suppressed kidney expression of Ifnb, Il6, Isg15, Ifit1, Ifit3, and Irf7.
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Animal Model:C57BL/6J (male and female; 6-8 weeks old)[1]
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Dosage:100, 300 mg/kg
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Administration:p.o.; once daily; for 7 consecutive days
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Result:Caused no behavioral abnormalities throughout the administration period, and body weight changes were comparable to the vehicle control group.
Produced no significant differences in the absolute weights of major organs including the heart, lungs, liver, spleen, and kidneys.
Induced no significant abnormal changes in serum biochemical parameters (ALT, AST, ALP, CK, LDH, BUN).
Showed no obvious tissue damage in major organs as revealed by histopathological (H&E) examination.
Chemical Information
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CAS No. 3105133-93-2
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Molecular Weight 502.46
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Formula C24H22F4N6O2
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SMILES
FC1=CC=C(C2=C1)NC=C2NC(NC3=NN4C(CN(CC4)CCC5=CC=C(C=C5)OC(F)(F)F)=C3)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
STING-IN-21 Related Classifications
HY-191414 Related Classifications
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