STING Degrader-3
STING Degrader-3 is a PROTAC-like STING degrader with a DC50 of 2.58 μM in THP-1 cells. STING Degrader-3 degrades STING protein via the lysosomal pathway. STING Degrader-3 functions as a non-degradative inhibitor in macrophages. STING Degrader-3 reduces the phosphorylation levels of TBK1 and IRF3, and downregulates the expression of IFN-β, CXCL10, IL-6, TNFα, IL-1β, ISG15 and ISG56. STING Degrader-3 exhibits renoprotective properties in a cisplatin-induced acute kidney injury model. STING Degrader-3 can be used in studies related to acute kidney injury. ((Pink: STING ligand (HY-168676); Blue: CRBN ligand (HY-126457); Black: linker (HY-W123015); CRBN ligand + linker: (HY-168677)).
For research use only. We do not sell to patients.
- Formula: C35H33N7O11
- Molecular Weight:727.68
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
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TBK1 |
IL-1β |
IL-6 |
STING Degrader-3 (Compound P8) (0.076-20 μM; 3-36 h) potently degrades STING protein in THP-1 cells, with a DC50 of 2.58 μM at 24 h, and exhibits time- and dose-dependent activity[1].
STING Degrader-3 (2.5-40 μM; 24 h) selectively degrades STING protein in THP-1 cells without affecting inflammation-related proteins STAT3 or AKT[1].
STING Degrader-3 (3-10 μM; 12-48 h) degrades STING protein in THP-1 cells via the lysosomal pathway (rather than the proteasomal pathway), without affecting STING mRNA levels, and STING protein expression recovers within 24 h after removal of the compound[1].
STING Degrader-3 (0.3-20 μM, 0-48 h) inhibits the activation of cGAMP (HY-12512)-induced STING downstream signaling pathway in THP-1 cells, reduces the phosphorylation levels of TBK1 and IRF3, and downregulates the mRNA levels of pro-inflammatory cytokines and interferon-stimulated genes[1].
STING Degrader-3 (0.3-30 μM; 24 h, 1 h pretreatment + 24 h stimulation) acts as a STING pathway inhibitor (rather than a degrader) in RAW264.7 cells. It reduces DMXAA (HY-10964)-induced downstream signal transduction and mRNA levels of proinflammatory mediators without altering STING protein levels[1].
STING Degrader-3 (0.33-90 μM; 48 h) exhibits low cytotoxicity in normal human HEK293T and HUVEC cells[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 cells
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Concentration:0.076, 0.15, 0.3, 0.625, 1.25, 2.5, 10, 20 μM
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Incubation Time:3, 6, 9, 12, 24, 36 h
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Result:Achieved 82% degradation of STING protein at 10 μM for 24 h.
Exhibited dose-dependent degradation with a DC50 of 2.58 μM after 24 h treatment.
Started degrading STING protein at 9 h and reached maximum degradation levels at 24 h.
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Cell Line:THP-1 cells
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Concentration:0.3, 1.2, 5, 20 μM
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Incubation Time:24 h pretreatment + 24 h cGAMP stimulation
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Result:Suppressed cGAMP-induced pTBK1 and pIRF3 expression in a concentration-dependent manner.
Dose-dependently reduced cGAMP-induced mRNA levels of IFN-β, IL-6, CXCL10, TNFα, ISG15, and ISG56.
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Cell Line:RAW264.7 cells
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Concentration:0.33, 1.1, 3.3, 10, 30 μM (STING protein analysis); 0.3, 1.2, 5, 20 μM (signaling assay)
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Incubation Time:24 h (STING protein analysis); 1 h pretreatment + 24 h DMXAA stimulation (signaling assay)
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Result:Did not induce STING protein degradation at concentrations up to 30 μM after 24 h treatment.
Suppressed DMXAA-induced pTBK1 and pIRF3 expression in a concentration-dependent manner.
Dose-dependently reduced DMXAA-induced mRNA levels of IFN-β, IL-6, CXCL10, and TNFα.
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Cell Line:human monocytic leukemia THP-1 cells
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Concentration:2.5, 5, 10, 20, 40 μM
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Incubation Time:24 h
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Result:Degraded STING protein in a concentration-dependent manner.
Did not reduce protein levels of STAT3 or AKT at any tested concentration.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Eight-week-old C57BL/6J male mice[1]
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Dosage:25, 50 mg/kg
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Administration:i.p., 1 h prior to Cisplatin injection
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Result:Alleviated Cisplatin-induced acute kidney injury in C57BL/6J mice, achieving a 100% survival rate.
Reduced levels of blood urea nitrogen, creatinine, and uric acid.
Downregulated the expression of IFN-β, CXCL10, IL-6, TNFα, IL-1β, ISG15, and ISG56.
Chemical Information
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Molecular Weight 727.68
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Formula C35H33N7O11
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SMILES
O=C1CCC(C(N1)=O)N2C(C3=CC=CC(OCC4=CN(N=N4)CCCCCC(OCCC5=CC=C(C=C5)NC(C6=CC=C(O6)[N+]([O-])=O)=O)=O)=C3C2=O)=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)