JAK2-IN-20
JAK2-IN-20 is an orally active dual inhibitor targeting JAK2 kinase (IC50=49.17 nM) and influenza A virus PB2 protein (IC50=3.337 μM, Kd=2.82 μM). JAK2-IN-20 effectively blocks the JAK/STAT signaling pathway by reducing the phosphorylation levels of STAT1 and STAT3, thereby inhibiting viral replication and downregulating the expression of viral NP and PB2 proteins. In addition, JAK2-IN-20 significantly inhibits the mRNA expression of key inflammatory cytokines such as IL-6, TNF-α and IFN-β in inflammation and influenza infection models. JAK2-IN-20 serves as an important tool molecule for the study of influenza A virus infection and related pathologies.
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- 화학식: C16H17F2N5O
- 분자량:333.34
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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JAK2 49.17 nM (IC50) |
JAK2-IN-20 (compound 4B) potently protects MDCK cells against damage induced by H1N1 influenza virus (EC50=14.71 nM) and inhibits the cap-binding activity of influenza A PB2 protein (IC50=3.337 nM)[1].
JAK2-IN-20 exhibits low cytotoxicity in multiple cell lines, with a CC50 of >100 μM (48 h) in MDCK cells[1].
JAK2-IN-20 (1 μM; 60 min; 37°C) exhibits excellent metabolic stability in mouse liver microsomes, with a half-life of 47.8 min and an intrinsic clearance (CLint) of 29.0 μL/min/mg[1].
JAK2-IN-20 (250-2000 nM) binds directly to the cap-binding domain of influenza A virus PB2, with a Kd value of 2.82 μM[1].
JAK2-IN-20 (5-10 μM; 30 min; 6 h) dose-dependently inhibits LPS (1 μg/mL)-induced expression of pro-inflammatory cytokines (IL-6, IL-1β) and IFN-β in RAW 264.7 macrophages, and exhibits potent activity at 10 μM[1].
JAK2-IN-20 (5-10 μM; 30 min; 6 h) potently inhibits the expression of poly (I:C)-induced proinflammatory cytokines (IL-6, TNF-α) and type I interferons (IFN-α, IFN-β) in RAW 264.7 macrophages at a concentration of 10 μM[1].
JAK2-IN-20 (250-500 nM; 24 h) inhibits the expression of H1N1 virus PB2 mRNA and reduces the levels of virus-induced proinflammatory cytokines (IL-6, TNF-α) in A549 cells at a concentration of 500 nM[1].
JAK2-IN-20 inhibits the JAK/STAT signaling pathway in both H1N1-infected A549 cells and IFN-β-stimulated THP-1 cells by reducing the phosphorylation levels of STAT1 and STAT3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LPS-induced RAW 264.7 macrophages
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Concentration:5 μM, 10 μM
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Incubation Time:30 min pre-LPS stimulation; 6 h post-stimulation
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Result:Reduced LPS-induced IL-6 mRNA levels by 1.5-fold, IL-1β mRNA levels by 6.3-fold, and IFN-β mRNA levels by 83% at 10 μM.
Reduced IFN-β mRNA levels by 55% at 5 μM, with attenuated effects on IL-6 and IL-1β.
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Cell Line:Poly(I:C)-induced RAW 264.7 macrophages
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Concentration:5 μM, 10 μM
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Incubation Time:30 min pre-poly(I:C) stimulation; 6 h post-stimulation
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Result:Reduced poly(I:C)-induced IL-6 mRNA levels by 4.8-fold, TNF-α mRNA levels by 3.0-fold, IFN-β mRNA levels by 44-fold, and IFN-α mRNA levels by 1.8-fold at 10 μM.
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Cell Line:H1N1-induced A549 cells
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Concentration:250 nM, 500 nM
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Incubation Time:24 h (added 1-2 h post-H1N1 infection)
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Result:Reduced H1N1-induced PB2 mRNA expression by 67%, IL-6 mRNA levels by 5.2-fold, and TNF-α mRNA levels by 2.5-fold at 500 nM, with moderate inhibition of IFN-α and IFN-β.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1[1]
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Dosage:3 mg/kg (i.v.); 30 mg/kg (p.o.)
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Administration:i.v.; single dose; p.o.; single dose
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Result:Achieved a Cmax of 1903 ng/mL, AUC0-t of 751 h ng/mL, T1/2 of 0.505 h, MRT0-t of 0.293 h, Vz of 2929 mL/kg, and Cl of 4011 mL/h/kg following intravenous administration.
Achieved a Cmax of 3513 ng/mL, AUC0-t of 7422 h ng/mL, T1/2 of 1.44 h, MRT0-t of 1.56 h, and oral bioavailability of 99.4% following oral administration.
Chemical Information
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분자량 333.34
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화학식 C16H17F2N5O
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SMILES
FC1=CC(C(C2=NC(N[C@@H](C)C(C)(C)O)=C(F)C=N2)=CN3)=C3N=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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