BMS-986126
BMS-986126 is a potent, selective, and orally active IRAK4 inhibitor (IC50 = 5.3 nM). BMS-986126 broadly inhibits MyD88-dependent signaling pathways. BMS-986126 demonstrates robust activity in the MRL/lpr and NZB/NZW murine models of lupus, inhibiting multiple pathogenic responses. BMS-986126 can be used for autoimmune diseases research, such as lupus erythematosus (SLE).
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- CAS No.: 1610017-20-3
- Formule: C22H25FN6O2
- Masse moléculaire:424.47
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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IRAK4 5.3 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| PBMC | IC50 |
0.048 μM
Compound: 28
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Inhibition of lipoteichoic acid-induced IL6 production in human PBMC incubated for 30 mins by ELISA method
Inhibition of lipoteichoic acid-induced IL6 production in human PBMC incubated for 30 mins by ELISA method
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[PMID: 25479567] |
BMS-986126 demonstrates similar, nanomolar potency (IC50: 135-456 nM) against multiple MyD88-dependent TLRs (TLR2/5/7/9) in human PBMCs, as well as potent inhibition of both NF-κB-regulated (IL-6) and type I IFN (IFN-α) responses, extending to cytokines induced by IL-1β and IL-18[1].
BMS-986126 fails to significantly affect cytokine production induced by the MyD88-independent agonists TLR3 and TNF-α[1].
BMS-986126 (0-2 μM, 30 min) dose-dependently inhibits the phosphorylation of IKKα/β and ERK downstream of TLR2 and TLR4, and ERK downstream of TLR7 in human PBMCs[1].
BMS-986126 demonstrates equivalent potency in inhibiting TLR7/9-induced interferon response gene expression (e.g., IFIT1) in PBMCs from both healthy donors and patients with SLE[1].
BMS-986126 (5 μM, 30 min) broadly reverses the gene expression profile induced by TLR7 activation in human PBMCs, with a significant proportion of the inhibited genes being canonical interferon-stimulated genes[1].
BMS-986126 (16-80 nM, 30 min) exhibits a synergistic effect with Prednisolone (HY-17463) in suppressing TLR9-induced and flu virus-induced IFIT1 expression in human PBMCs, showing significantly greater inhibition than either single agent[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:PBMCs
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Concentration:0, 0.07, 0.22, 0.67, 2 μM
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Incubation Time:30 min
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Result:Inhibited LPS-induced IKKα/b and ERK phosphorylation.
Inhibited TLR2-induced IKKα/b and ERK phosphorylation.
Robustly inhibit Gardiquimod (HY-103697)-induced ERK phosphorylation
BMS-986126 (0.3-10 mg/kg, p.o., daily for 6 days or 8 weeks) significantly inhibits disease activity in both spontaneous (MRL/lpr and NZB/NZW) murine lupus models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c mice intraperitoneally injected with LTA (25 mg/kg)[1]
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Dosage:0.1, 0.3, 1.0, and 3.0 mg/kg
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Administration:p.o., single dose 30 min pre-LTA
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Result:Dose-dependently suppressed LTA-induced IL-6 plasma levels, with maximal inhibition observed at the top dose of 3 mg/kg.
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Animal Model:Male C57BL/6 mice (12-week-old) intravenously injected with CpG-ODN (2.5 μg)[1]
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Dosage:1 and 3 mg/kg
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Administration:p.o., single dose 30 min pre-CpG-ODN
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Result:Strongly suppressed IFN-α at both 2 and 8 h after CpG-ODN challenge.
No IFN-α was detected in any group at 24 h after CpG-ODN challenge.
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Animal Model:Male C57BL/6 mice (12-week-old) intraperitoneally injected with Gardiquimod (5 mg/kg)[1]
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Dosage:1 and 3 mg/kg
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Administration:p.o., single dose 30 min pre-Gardiquimod
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Result:Dose-dependently suppressed both IFN-α and IL-6 production at both 2 and 8 h after Gardiquimod challenge.
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Animal Model:Male MRL/lpr mice (12-14 weeks old)[1]
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Dosage:0.3, 1, 3, and 10 mg/kg
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Administration:p.o., daily for 8 weeks
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Result:Dose-dependently suppressed biomarkers of kidney damage and systemic inflammation.
Showed very strong inhibition of kidney damage end points, including reduction of absolute protein levels in the urine, urine NGAL levels, and serum blood urea nitrogen.
Demonstrated significant protection of all end points at 1 mg/kg.
Dose-dependently suppressed dsDNA-specific autoantibody titers, as well as plasma levels of IL-10 and IL-12p40.
Significantly suppressed the percentage of splenic IFN-α+ pDCs at both the 1 and 10 mg/kg doses.
Suppressed IL-6 production by splenic CD11b+ myeloid cells.
All but the lowest dose inhibited IgG deposition in the kidney.
Dose-dependently suppressed histopathology in the kidney.
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Animal Model:Male C57BL/6 mice induced by Imiquimod (HY-B0180)[1]
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Dosage:0.3, 1, 3, and 10 mg/kg
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Administration:p.o., daily for 6 days
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Result:Dose-dependently suppressed skin thickening, scaling, erythema, and spleen weight gain.
Significantly inhibited skin histopathology at 3 and 10 mg/kg.
Maintained its plasma levels above the mouse in vitro whole blood LTA-induced IL-6 IC50 value for 24 h.
Maintained its concentrations above the mouse whole blood IC50 value (LTA-induced IL-6 IC50) for 8-12 h out of the day.
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Animal Model:Female NZB/NZW mice (12-14 weeks old)[1]
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Dosage:0.3, 1, 3, and 10 mg/kg
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Administration:p.o., daily for 25 weeks
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Result:Strongly suppressed biomarkers of kidney damage at all doses tested, including urine protein levels and urine levels of NGAL.
Dose-dependently suppressed systemic end points including dsDNA-specific autoantibody titers and plasma IL-12p40 levels.
Inhibited the percentage of splenic IFN-α+ pDCs.
Significantly inhibited the expression of the IFN response gene IFIT1 in peripheral blood.
Dose-dependently inhibited IgG deposition in the kidney.
Significantly suppressed histopathology in the kidneys with profound effects on glomerular damage and tubular damage subscores.
Chemical Information
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CAS No. 1610017-20-3
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Masse moléculaire 424.47
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Formule C22H25FN6O2
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SMILES
CC(C)(O)[C@H](F)CNC(C(C(NC1CC1)=C2)=CN=C2NC3=NC4=C(C=NC=C4)C=C3)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BMS-986126 Related Classifications
HY-124995 Related Classifications
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