JH-I-25
JH-I-25 is an orally active IRAK1 and IRAK4 inhibitor. JH-I-25 inhibits LPS-induced IRAK4 phosphorylation, IRAK1 degradation, MAPK activation, and the expression of proinflammatory cytokines TNF-α and IL-6 in lung tissues. JH-I-25 improves the survival rate of LPS-induced septic mice and serves as an IRAK4 recruiter in the design of proteolysis-targeting chimeric molecules. JH-I-25 can be used in research related to diffuse large B-cell lymphoma, Waldenström's macroglobulinemia, septic shock, rheumatoid arthritis, atherosclerosis, Alzheimer's disease, acute lung injury, sepsis, and psoriasis.
For research use only. We do not sell to patients.
- CAS No.: 1042673-20-0
- Formula: C20H21N5O3
- Molecular Weight:379.42
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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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Help & FAQs
Biological Activity
Description
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IRAK1 |
IRAK4 |
IL-6 |
TNF-α |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HBL1 | IC50 |
2.8 μM
Compound: JH-I-25
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Cytotoxicity against human HBL1 cells assessed as cell growth inhibition measured after 12 days by WST-8 assay
Cytotoxicity against human HBL1 cells assessed as cell growth inhibition measured after 12 days by WST-8 assay
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[PMID: 34279092] |
In Vitro
JH-I-25 (500 nM; 24 h) inhibits IRAK4 kinase activity and the downstream MAPK signaling pathway in LPS (HY-D1056)-stimulated RAW 264.7 cells, but fails to block the activation of the NF-κB pathway due to its inability to disrupt the scaffolding function of IRAK4[2].
JH-I-25 (pretreatment with 1 μM for 6 h followed by E. coli stimulation for 6 h) reduces the E. coli-induced expression and production of inflammatory cytokines in RAW264.7 cells[3].
JH-I-25 (500 nM; 1 h) inhibits the production of inflammatory cytokines in LPS-stimulated RAW 264.7 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LPS-stimulated RAW 264.7 mouse macrophage cells
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Concentration:500 nM (pre-incubated for 24 h before 1 h LPS stimulation); 500 nM (pre-incubated for 24 h before LPS stimulation for 0, 15, 30, 60, 120, 180 min)
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Incubation Time:24 h (pre-incubation before 1 h LPS stimulation); 24 h (pre-incubation before LPS stimulation for 0, 15, 30, 60, 120, 180 min)
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Result:Effectively inhibited the phosphorylation of IRAK4.
Suppressed LPS-induced IRAK1 degradation.
Blocked phosphorylation of the MAPK pathway components ERK and p38.
Did not block LPS-induced IκB-α degradation, which occurred as early as 15 min in treated cells.
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Cell Line:LPS-stimulated RAW 264.7 mouse macrophage cells
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Concentration:500 nM (pre-treated for 1 h before 6 h LPS stimulation)
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Incubation Time:1 h (pre-treatment before 6 h LPS stimulation)
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Result:Reduced the transcription of Il6 and Tnfα.
Exhibited a less pronounced inhibitory effect compared to KT-474.
In Vivo
JH-I-25 (20 mg/kg; p.o.; twice daily; administration initiates 12 hours prior to LPS challenge and continues until the end of the experiment) improves the survival rate of C57BL/6 mice in the LPS-induced sepsis model[2].
JH-I-25 (20 mg/kg; p.o.; twice daily; for 6 consecutive days) exerts a protective effect in an imiquimod (HY-B0180)-induced mouse psoriasis model[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (~20 g)[2]
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Dosage:20 mg/kg
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Administration:i.g.; single dose; 12 hours prior to LPS challenge
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Result:Reduced LPS-induced TNF-α and IL-6 expression in lung tissues.
Significantly inhibited in vivo MAPK signaling via reduced p-p38 levels.
Did not inhibit IκB-α degradation or NFκB p65 phosphorylation in lung tissue.
Reduced total cell counts in BALF.
Lowered lung wet/dry weight ratio.
Decreased F4/80-positive macrophage accumulation in lung tissue compared to LPS-only mice.
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Animal Model:C57BL/6[2]
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Dosage:20 mg/kg
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Administration:i.g.; twice daily; starting 12 hours prior to LPS challenge and continuing through experimental period
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Result:Resulted in a significantly higher 7-day survival rate compared to LPS-only sepsis model mice.
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Animal Model:C57BL/6 (male, daily application of 3.125 mg/mouse imiquimod cream to shaved back skin for 6 days)[3]
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Dosage:20 mg/kg
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Administration:p.o.; twice daily; 6 days
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Result:Improved clinical signs of psoriasis (reduced erythema, scaling, and skin thickness) compared to vehicle-treated controls.
Showed less improvement than LC-MI-3.
Attenuated imiquimod-induced increases in spleen weight.
Had no effect on mouse body weight.
Chemical Information
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CAS No. 1042673-20-0
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Molecular Weight 379.42
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Formula C20H21N5O3
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SMILES
O=C(NC1=CC=C(C=C1OC)N2CCOCC2)C3=NC(=CC=C3)C4=NNC=C4
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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
[1]. Wang L, et al. Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor-associated kinase 4 (IRAK4). The Journal of biological chemistry. 2019 Mar 22;294(12):4511-4519. [Content Brief]
[3]. Chen L, et al. Discovery of LC-MI-3: A Potent and Orally Bioavailable Degrader of Interleukin-1 Receptor-Associated Kinase 4 for the Treatment of Inflammatory Diseases. Journal of medicinal chemistry. 2024 May 23;67(10):8060-8076. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JH-I-25 Related Classifications
HY-138834 Related Classifications
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