IRAK4-IN-35
IRAK4-IN-35 is an orally active IRAK4 inhibitor with an IRAK4 IC50 of 9.88 nM. IRAK4-IN-35 also inhibits JAK3, EGFR, CDK2 with IC50 values of 6.72 nM, 32.35 nM, and 39.08 nM, respectively. IRAK4-IN-35 inhibits the production of proinflammatory cytokines, blocks inflammatory signaling pathways, and reduces serum TNF-α levels and spleen index in mouse models of acute inflammation. IRAK4-IN-35 decreases the disease activity index, paw swelling degree, and spleen index in a collagen-induced arthritis mouse model. IRAK4-IN-35 can be used for the research of rheumatoid arthritis.
For research use only. We do not sell to patients.
- CAS No.: 3112339-39-3
- Formula: C25H21N5O2
- Molecular Weight:423.47
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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
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
IRAK4 9.88 nM (IC50) |
JAK3 6.72 nM (IC50) |
CDK2 39.08 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| THP-1 | IC50 |
0.02 μM
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Inhibition of LPS-induced TNF-α release in differentiated THP-1 cells incubated for 24 h.
Inhibition of LPS-induced TNF-α release in differentiated THP-1 cells incubated for 24 h.
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42593912 |
| THP-1 | CC50 |
0.15 μM
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Cytotoxicity against differentiated THP-1 cells assessed by CellTiter-Glo viability assay after 24 h incubation.
Cytotoxicity against differentiated THP-1 cells assessed by CellTiter-Glo viability assay after 24 h incubation.
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42593912 |
In Vitro
IRAK4-IN-35 (Compound 43) (1 h) potently inhibits the kinase activity of purified recombinant IRAK4, with an IC50 of 9.88 nM[1].
IRAK4-IN-35 (50 nM) significantly inhibits the activation of IRAK4-mediated NF-κB and MAPK signaling pathways in LPS-induced differentiated THP-1 cells[1].
IRAK4-IN-35 (24 h) inhibits LPS-induced TNF-α release in differentiated THP-1 cells with an IC50 of 0.02 μM; the compound has a cytotoxic CC50 of 0.15 μM, yielding a selectivity index of 8.46[1].
IRAK4-IN-35 (2 h) inhibits R848 (HY-13740)-induced TNF-α and IL-6 secretion in primary human peripheral blood mononuclear cells (PBMCs) in a concentration-dependent manner, with activity comparable to or better than that of PF-06650833 (HY-19836)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
IRAK4-IN-35 (10 mg/kg; p.o.; twice daily; 14 days) effectively ameliorates symptoms in a collagen-induced arthritis mouse model, reducing disease activity, paw swelling, and spleen index[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 20−22 g)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.; single dose
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Result:Significantly reduced serum TNF-α levels compared to the vehicle group.
Reduced spleen index at the 50 mg/kg dose compared to the vehicle group.
Markedly inhibited IRAK4 phosphorylation in spleen homogenates at the 50 mg/kg dose.
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Animal Model:DBA/1 (male, 8 weeks old)[1]
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Dosage:10 mg/kg
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Administration:p.o.; twice daily; 14 days
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Result:Significantly reduced disease activity index scores compared to the vehicle group.
Reduced hindfoot swelling compared to the vehicle group.
Lowered the spleen index compared to the vehicle group.
Demonstrated efficacy comparable to the positive control PF-06650833 at the same dose.
Chemical Information
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CAS No. 3112339-39-3
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Molecular Weight 423.47
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Formula C25H21N5O2
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SMILES
O=C1NC2=C(C=C(C3=NC(N[C@H](C4=CC=CC=C4)CO)=CN=C3)C=C2)/C1=C/C5=CC=CN5
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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)
IRAK4-IN-35 Related Classifications
HY-187692 Related Classifications
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