LC-MI-3
LC-MI-3 is an orally active IRAK4 degrader with an IC50 of 57.2 nM and high selectivity among human protein kinases.LC-MI-3 eliminates IRAK4 kinase and scaffolding functions via the cereblon E3 ubiquitin ligase and ubiquitin-proteasome systems.LC-MI-3 inhibits downstream nuclear factor-κB and IRAK4-mediated inflammatory signaling pathways.LC-MI-3 exerts anti-inflammatory activity in lipopolysaccharide-, Escherichia coli-, TLR4-, and TLR7-induced inflammatory models.LC-MI-3 can be used for the research of acute lung injury, sepsis, psoriasis, and inflammatory diseases.
(Pink: IRAK4 ligand (HY-179095); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3053823-69-8
- Formula: C39H36N8O8
- Molecular Weight:744.75
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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
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Biological Activity
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IRAK4 57.2 nM (IC50) |
LC-MI-3 potently inhibits IRAK4 kinase activity in cell-free biochemical assays, with an IC50 of 57.2 nM.[1]
LC-MI-3 (100 nM; 12 h) degrades 85% of IRAK4 protein in BaF3-TEL-IRAK4 cells[1].
LC-MI-3 (20-2500 nM; 12 h) induces dose-dependent degradation of IRAK4 in RAW264.7 cells, with a DC50 of 47.38 nM and a Dmax of 91%[1].
LC-MI-3 (100 nM) significantly reduces the level of IRAK4 in human peripheral blood mononuclear cells (PBMCs)[1].
LC-MI-3 (1 μM) exhibits high selectivity for IRAK4 in cell-free 468-kinome profiling, with only 3 additional kinases showing an inhibition rate >95%[1].
LC-MI-3 (200 nM; 12 h) selectively downregulates IRAK4 protein levels in RAW264.7 cells without degrading the off-target proteins RIOK1, IKZF1, IKZF3 or SALL4[1].
LC-MI-3 (1 μM; 1 h) potently inhibits Lipopolysaccharides (LPS) (HY-D1056)-induced phosphorylation of ERK in RAW264.7 cells[1].
LC-MI-3 (1 μM; 1 h) significantly inhibits LPS-induced NF-κB activity in RAW264.7-NF-κB-RE-EGFP cells[1].
LC-MI-3 (1 μM; 1 h) blocks LPS-induced phosphorylation of p65 and inhibits the degradation of IκB-α in RAW264.7 cells[1].
LC-MI-3 (1 μM; 1 h) significantly reduces LPS-induced nuclear translocation of NF-κB p65 in RAW264.7 cells[1].
LC-MI-3 (6 h) slightly reduces LPS-induced TLR4 endocytosis in RAW264.7 cells[1].
LC-MI-3 potently degrades IRAK4 in RAW264.7 cells, with a DC50 of 47.3 nM[2].
LC-MI-3 exhibits high selectivity for IRAK4 in profiling against 468 human protein kinases and the proteome[2].
LC-MI-3 potently degrades IRAK4 in HEK293T cells, with a DC50 of 47.3 nM[3].
LC-MI-3 (1 μM; 1 h) significantly inhibits LPS-induced NF-κB activity in RAW264.7-NF-κB-RE-EGFP cells[1].
LC-MI-3 (1 μM; 1 h) significantly reduces LPS-induced IL-6 and TNFα mRNA expression levels in RAW264.7 cells[1].
LC-MI-3 (1 μM; 1 h) significantly reduces LPS-induced IL-6 and TNF-α secretion in RAW264.7 cells[1].
LC-MI-3 (1 μM; 6 h) significantly inhibits E. coli-induced IL-6 and TNFα mRNA expression in RAW264.7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BaF3-TEL-IRAK4 cells
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Concentration:100 nM
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Incubation Time:12 h
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Result:Reduced total IRAK4 levels to 15% of control levels, corresponding to an 85% degradation rate.
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Cell Line:RAW264.7 cells
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Concentration:20 nM; 40 nM; 80 nM; 160 nM; 312 nM; 625 nM; 1250 nM; 2500 nM
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Incubation Time:12 h
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Result:Induced dose-dependent degradation of IRAK4, with a half-maximal degradation concentration (DC50) of 47.38 nM and a maximum degradation (Dmax) of 91%.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:1 h
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Result:Potently inhibited LPS-induced ERK phosphorylation, reducing the relative density of p-ERK/ERK to levels significantly lower than LPS-treated cells.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:1 h
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Result:Blocked LPS-induced p65 phosphorylation and completely inhibited LPS-induced IκB-α degradation across all time points.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:1 h
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Result:Significantly reduced LPS-induced p65 nuclear translocation, with Pearson's correlation coefficient significantly lower than LPS-treated cells.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:1 h
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Result:Significantly normalized LPS-induced increases in il6 and tnfα mRNA expression, reducing levels to values significantly lower than LPS-treated cells.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:1 h
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Result:Significantly reduced LPS-induced IL-6 and TNF-α secretion, with cytokine concentrations significantly lower than LPS-treated cells.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:6 h
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Result:Significantly suppressed E. coli-induced increases in IL-6 and TNF-α mRNA expression, with levels significantly lower than E. coli-treated cells.
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Cell Line:RAW264.7 cells
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Concentration:1 μM
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Incubation Time:6 h
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Result:Significantly suppressed E. coli-induced IL-6 and TNF-α secretion, with cytokine concentrations significantly lower than E. coli-treated cells.
LC-MI-3 (20 mg/kg; p.o.; twice daily; 6 days) exerts robust therapeutic effects in an imiquimod-induced psoriasis model in C57BL/6 mice, with superior efficacy to the IRAK4 kinase inhibitor JH-I-25[1].
LC-MI-3 (20 mg/kg; p.o.; twice daily; 6 days) provides significant protection against E. coli-induced septic death in C57BL/6 mice, resulting in a higher survival rate than the IRAK4 kinase inhibitor JH-I-25[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, 8 weeks old, 20 g)[1]
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Dosage:20 mg/kg
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Administration:p.o.; single dose
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Result:Significantly reduced LPS-induced IL-6 and TNF-α concentrations in BALF.
Normalized il6 and tnfα mRNA levels in lung tissue.
Prevented LPS-induced structural disruption of lung tissue.
Reduced F4/80-positive macrophage infiltration in lung tissue.
Blocked LPS-induced phosphorylation of NF-κB p65 and ERK.
Inhibited LPS-induced IκB-α degradation in lung tissue.
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Animal Model:C57BL/6 (male, 8 weeks old, 20 g)[1]
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Dosage:20 mg/kg
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Administration:p.o.; twice daily; 6 days
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Result:Significantly improved survival of E. coli-challenged mice, with a higher survival rate than the JH-I-25-treated group at 200 hours post-challenge.
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Animal Model:C57BL/6 (male, 20 g)[1]
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Dosage:20 mg/kg
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Administration:p.o.; twice daily; 6 days
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Result:Significantly improved clinical signs of psoriasis, reducing imiquimod-induced swelling, scaling, and erythema scores more effectively than JH-I-25.
Attenuated keratinocyte proliferation, epidermal acanthosis, mastoid processes, and dermal inflammatory cell infiltration.
Reduced spleen weight and skin thickness.
Showed no effect on mouse body weight.
Chemical Information
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CAS No. 3053823-69-8
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Molecular Weight 744.75
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Formula C39H36N8O8
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SMILES
O=C1N(C(C2=C1C=C(C=C2)C#CCOCCC(N3CCN(CC3)C4=CC=C(C(OC)=C4)NC(C5=CC=CC(C6=CC=NN6)=N5)=O)=O)=O)C7CCC(NC7=O)=O
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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]. 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]
[2]. Lin Y, et al. Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degraders for Treating Inflammatory Diseases: Advances and Prospects. Journal of medicinal chemistry. 2025 Jan 23;68(2):902-914. [Content Brief]
[3]. Fan Y, et al. Discovery of Rigid Linker-Based IRAK4 PROTACs with Improved Metabolic Stability for the Treatment of Inflammatory Diseases. Journal of medicinal chemistry. 2025 Aug 28;68(16):17874-17896. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LC-MI-3 Related Classifications
HY-162538 Related Classifications
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