SMU-3k
SMU-3k is a STING activator and PD-L1 inhibitor, with a PD-L1 IC50 of 106 nM, a KD of 386 nM for human PD-L1, and a KD of 352 nM for murine PD-L1. SMU-3k activates the STING pathway, induces phosphorylation of TBK1 and IRF3, and promotes the expression of IFN-β, IL-6 and CXCL10. SMU-3k blocks the PD-1/PD-L1 interaction, reduces PD-L1 levels and induces PD-L1 internalization. Through dual immunomodulation, SMU-3k exerts synergistic tumor growth inhibitory effects in a mouse colon cancer model. SMU-3k can be used for the research of colon cancer.
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- Fòrmula: C57H59ClN4O10S
- Peso molecular:1027.62
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
IL-6 |
In Vitro
SMU-3k (20 μM; 24 h) potently activates STING signaling in THP1-Blue-ISG cells with an EC50 of 9.35 μM, achieving a 23-fold activation at 20 μM[1].
SMU-3k (1 μM; 1 h) potently inhibits the PD-1/PD-L1 interaction with an IC50 of 106 nM, achieving 82% inhibition at 1 μM[1].
SMU-3k (10-50 μM) induces concentration-dependent upregulation of IFN-β, IL-6, and CXCL10 mRNA levels in THP1-Blue-ISG cells, with the strongest induction observed at 50 μM[1].
SMU-3k (11-33 μM; 24 h) induces concentration-dependent secretion of IFN-β in THP-1 cells[1].
SMU-3k (10-50 μM; 4 h) induces concentration-dependent phosphorylation of TBK1 and IRF3 in THP1-Blue-ISG cells, confirming activation of the STING signaling pathway[1].
SMU-3k (0.19-50 μM; 48 h) alleviates PD-L1-mediated immunosuppression and restores T-cell-mediated cytotoxicity toward HepG2 cells with an IC50 of 10.6 μM[1].
SMU-3k (1-10 μM) reduces PD-L1 protein levels in MB231 cells in a concentration-dependent manner[1].
SMU-3k (10 μM; 3-24 h) induces time-dependent internalization of PD-L1 from the plasma membrane to intracellular compartments in PD-L1-GFP-transfected 293T cells, with nearly complete internalization after 24 h at 10 μM[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:11, 33 μM
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Incubation Time:24 h
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Result:Induced IFN-β secretion to ~1 pg/mL at 11 μM, and to ~2 pg/mL at 33 μM, with statistically significant differences compared to control.
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Cell Line:THP1-Blue-ISG cells
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Concentration:10, 25, 50 μM
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Incubation Time:4 h
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Result:Induced concentration-dependent increases in phosphorylation of TBK1 and IRF3, with the strongest phosphorylation observed at 50 μM.
Kept total TBK1 and IRF3 levels unchanged across treatments.
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Cell Line:HepG2/Jurkat T cell coculture
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Concentration:0.19, 0.39, 0.78, 1.56, 3.12, 6.25, 12.5, 25, 50 μM
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Incubation Time:48 h
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Result:Restored T-cell-mediated cytotoxicity toward HepG2 cells in a concentration-dependent manner, with an IC50 of 10.6 μM.
Reduced HepG2 cell viability to ~20% of control levels at 50 μM.
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Cell Line:PD-L1-GFP-transfected 293T cells
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Concentration:10 μM
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Incubation Time:3, 6, 12, 24 h
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Result:Induced progressive redistribution of PD-L1 from the plasma membrane to intracellular compartments in a time-dependent manner, with nearly complete internalization observed after 24 h of treatment.
Parmacokinetics
| Species | Dose | Route | Tmax | T1/2 | Cmax | AUC0-12 |
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| Mice[1] | 2 mg/kg | i.v. | 0.03 h | 4.33 h | 15,897.33 ng/mL | 2197.54 ng·h/mL |
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/6 (6-8 weeks old)[1]
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Dosage:50 mg/kg; 75 mg/kg
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Administration:i.p.; once every 3 days; 6 total doses
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Result:Significantly reduced tumor growth compared to vehicle control, with greater efficacy than equivalent molar doses of MSA-2 monotherapy or BMS-1198 monotherapy, and comparable efficacy to the physical combination of MSA-2 and BMS-1198.
Produced even more pronounced tumor regression at 75 mg/kg.
Increased intratumoral CD4+ T cells to 38.4%, CD8+ T cells to 26.9%, and NK1.1+ cells to 34.4% at 50 mg/kg compared to control levels of 2.81%, 3.57%, and 12.1% respectively.
Showed no significant body weight loss during treatment.
Revealed no overt pathological alterations in heart, liver, spleen, and kidney via H&E staining at either dose.
Chemical Information
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Peso molecular 1027.62
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Fòrmula C57H59ClN4O10S
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SMILES
CC1=C(C=CC=C1C2=CC3=C(OCCO3)C=C2)COC4=C(C=C(C(OCC5=CC=CC(C#N)=C5)=C4)CN6C(CCCC6)C(N7CCN(CC7)CCOC(CCC(C8=CC9=CC(OC)=C(C=C9S8)OC)=O)=O)=O)Cl
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SMU-3k Related Classifications
HY-183607 Related Classifications
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