MFT251
MFT251 is a TBK1 activator. MFT251 directly activates TBK1, increasing kinase activity, IRF3 phosphorylation, and type I interferon and interferon-stimulated gene expression, thereby enhancing macrophage/dendritic cell activation, phagocytosis, and nitric oxide (NO) release, and inhibiting coronavirus replication. MFT251 can be used in research on melanoma and coronavirus infection (including SARS-CoV-2).
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- CAS. Nr.: 946305-51-7
- Formel: C21H16N2O5S
- Molecular Weight:408.43
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
TBK1 |
In Vitro
MFT251 (0.1-5 μM; 1 h at room temperature) enhances recombinant TBK1 kinase activity[1].
MFT251 (10 μM; 4-24 h) induces type I IFN and ISG transcription in THP-1 cells, with IFIT1 and MX1 upregulated more than 1,000-fold after 24 h of exposure at 10 μM[1].
MFT251 (10 μM; 0-12 h) induces STAT1/2 phosphorylation and IFIT1 protein expression in THP-1 cells[1].
MFT251 (10 μM) induces the expression of MX1, IFIT1, and OAS1 in THP-1, A549, MRC-5, Huh7, and HAP1 cells[1].
MFT251 (10 μM) acts through the TBK1-IRF3-IFNAR2 axis in HAP1 cells, as knockout of TBK1, IRF3, and IFNAR2 abolishes its ISG-inducing effect at 10 μM[1].
MFT251 (10 μM; 4-12 h) induces a multi-stage transcriptional program centered on IFN-β in THP-1 cells, with 1,277 genes upregulated throughout the time course[1].
MFT251 (24 h) activates BMDM and BMDC into a pro-inflammatory state and induces IFN-β after 24 h of exposure[1].
MFT251 (2 μM) induces IFIT1 in HAP1 wild-type cells and inhibits HCoV-229E replication, whereas the antiviral inhibitory effect requires IFNAR2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293 cells
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Concentration:20 μM
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Incubation Time:4 h + 20 h
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Result:Strongly induced all three readouts, p-IRF3, IFIT1, and MX1, across the 110 compounds screened.
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Cell Line:THP-1 cells
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Concentration:10 μM
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Incubation Time:4, 8, 12 h (time-course); 24 h (ISGs)
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Result:Induced IFN-α and IFN-β within 4 h; IFN-β was most strongly induced, with levels peaking at 4 h and declining up to 12 h.
IFN-λ was also induced.
ISGs IFIT1, MX1, IFITM1, ISG15, and OAS1 were upregulated; IFIT1 and MX1 showed > 1,000-fold increases after 10 μM exposure for 24 h.
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Cell Line:THP-1 cells
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Concentration:10 μM
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Incubation Time:2, 4, 6, 8, 12 h
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Result:p-STAT2 and p-STAT1 phosphorylation was detected from 4 h through 12 h after exposure.
IFIT1 protein induction was detected at 8 and 12 h.
Total STAT1 and STAT2 levels were monitored.
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Cell Line:MRC-5 cells
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Concentration:0.5 μM (HCoV-229E replication); 1, 5, 10 μM (plaque assay)
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Incubation Time:4 h pre-incubation + 2 h infection + 3-5 days overlay
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Result:Suppressed HCoV-229E replication by > 70% at 0.5 μM.
In plaque assays, tested at 1, 5, and 10 μM.
Strongly induced IFIT1 and reduced viral counts; antiviral activity was confirmed with HCoV-OC43.
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Cell Line:B16F10 melanoma cells
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Concentration:1 or 5 μM
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Incubation Time:24 h
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Result:Did not induce measurable apoptosis or necrosis at either 1 or 5 μM.
Parmacokinetics
| Species | Dose | Route | T1/2 | C0 | AUCall | AUCinf | CL | Vss |
|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 10.66 h | 858.31 ng/mL | 214.59 ng/mL·h | 236.15 ng/mL·h | 71.27 mL/min/kg | 16.28 L/kg |
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[1]
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Dosage:0.1 mg/kg; 0.2 mg/kg
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Administration:intratumoral; once daily for 7 days then every other day for total 30 days; once daily for 7 days; single injection
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Result:Substantially reduced tumor growth and increased survival by over 50% at 0.1 or 0.2 mg/kg.
Led to an almost 2-fold increase in IFN-β-producing monocytes within CD11c+ immune cells, with F4/80+ presenting monocytes particularly enriched.
Intratumoral macrophages increased by > 10%, dendritic cells by > 10%, and T cells by ∼5%.
Proinflammatory CD80+ activated macrophages (F4/80+/CD80+) increased 2-fold, while immunosuppressive CD206+ macrophages were reduced by 40%.
The activated dendritic cell population (CD11c+CD80+) increased by more than 2-fold compared with control tumors.
Tumor-infiltrating dendritic cells displayed increased presentation of the tumor antigen peptide SIINFEKL on MHC class I H-2Kb molecules.
CD8+ cytotoxic T cells within tumors increased by 2-to 3-fold, and tumor antigen-specific cytotoxic T cells more than doubled.
The percentage of PD-1 + T cells among tumor-infiltrating T cells declined by ∼30%.
Elicited robust local cytokine production-including IFN-β, IL-6, and IL-1β-within the tumor, while systemic serum levels remained minimal or undetected.
Chemical Information
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CAS. Nr. 946305-51-7
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Molecular Weight 408.43
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Formel C21H16N2O5S
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SMILES
O=C(C1=CC=C(C(NC2=NC(C3=CC4=C(C=C(C=C4)OC)O3)=CS2)=O)C=C1)OC
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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