MNK1/2-IN-10
MNK1/2-IN-10 is an orally active, selective MNK1/MNK2 inhibitor, with an IC50 of 10.84 nM for MNK1 and an IC50 of 12.81 nM for MNK2. MNK1/2-IN-10 inhibits eIF4E phosphorylation, the NF-κB signaling pathway, macrophage polarization, oxidative stress and the production of pro-inflammatory cytokines. MNK1/2-IN-10 alleviates kidney and spleen damage in LPS (HY-D1056)-induced inflammatory mouse models. Anti-inflammatory agent 115 is applicable for research related to acute inflammation.
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- Formule: C25H24N6O3S2
- Masse moléculaire:520.63
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Stockage:
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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Activité biologique
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Chemical Information
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- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
MNK1 10.84 nM (IC50) |
MNK2 12.81 nM (IC50) |
In Vitro
MNK1/2-IN-10 (Compound 13) (48 h) shows low cytotoxicity in RAW 264.7, HEK293T, HUVECs and AML-12 cell lines, with IC50 values ranging from 24.25 to 77.56 μM after 48 h of incubation[1].
MNK1/2-IN-10 (1.25-10 μM; 24 h) inhibits LPS-induced expression of p-eIF4E and iNOS in RAW 264.7 cells in a concentration-dependent manner[1].
MNK1/2-IN-10 (1.25-10 μM; 4 h) concentration-dependently inhibits the LPS-induced expression of p-eIF4E in RAW 264.7 cells[1].
MNK1/2-IN-10 (1.25-10 μM; 24 h) inhibits LPS-induced release of IL-6, TNF-α and MCP-1 in RAW 264.7 cells in a concentration-dependent manner[1].
MNK1/2-IN-10 (1.25-10 μM; 24 h) inhibits lipopolysaccharide (LPS)-induced nitric oxide release in RAW 264.7 cells in a concentration-dependent manner, with the maximum inhibitory effect observed at 10 μM[1].
MNK1/2-IN-10 (10 μM; 24 h) inhibits LPS-induced iNOS expression in RAW 264.7 cells[1].
MNK1/2-IN-10 (1.25-10 μM; 12 h) inhibits LPS-induced activation of the NF-κB pathway in RAW 264.7 cells in a concentration-dependent manner in vitro[1].
MNK1/2-IN-10 (10 μM; 24 h) inhibits LPS-induced nuclear translocation of P65 in RAW 264.7 cells[1].
MNK1/2-IN-10 (2.5-10 μM; 13 h) reduces LPS-induced ROS production in RAW 264.7 cells in a concentration-dependent manner[1].
MNK1/2-IN-10 (10 μM; 14 h) inhibits LPS-induced ROS production in RAW 264.7 cells[1].
MNK1/2-IN-10 (2.5-10 μM; 24 h) restores GSH levels and enhances SOD activity in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner in vitro[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW 264.7
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Concentration:10 μM, 5 μM, 2.5 μM, 1.25 μM
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Incubation Time:24 h
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Result:Suppressed LPS-induced phosphorylation of eIF4E in a concentration-dependent manner, with maximal suppression at 10 μM.
Suppressed LPS-induced expression of iNOS in a concentration-dependent manner, with maximal suppression at 10 μM.
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Cell Line:RAW 264.7
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Concentration:10 μM, 5 μM, 2.5 μM, 1.25 μM
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Incubation Time:2 h (pretreatment); 2 h (LPS stimulation)
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Result:Inhibited LPS-induced p-eIF4E expression in a concentration-dependent manner, as shown by reduced green fluorescence intensity.
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Cell Line:RAW 264.7
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Concentration:10 μM, 5 μM, 2.5 μM, 1.25 μM
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Incubation Time:24 h
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Result:Inhibited LPS-induced secretion of IL-6 in a dose-dependent manner.
Inhibited LPS-induced secretion of TNF-α in a dose-dependent manner.
Inhibited LPS-induced secretion of MCP-1 in a dose-dependent manner.
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Cell Line:RAW 264.7
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Concentration:10 μM
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Incubation Time:24 h
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Result:Diminished iNOS signal in the cytoplasm of LPS-stimulated cells.
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Cell Line:RAW 264.7
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Concentration:10 μM, 5 μM, 2.5 μM, 1.25 μM
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Incubation Time:12 h
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Result:Inhibited LPS-induced phosphorylation of P65 in a concentration-dependent manner.
Inhibited LPS-induced phosphorylation of IκBα in a concentration-dependent manner.
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Cell Line:RAW 264.7
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Concentration:10 μM
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Incubation Time:12 h (pretreatment); 12 h (LPS stimulation)
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Result:Blocked LPS-triggered nuclear translocation of P65, with significantly reduced fluorescence intensity in the nucleus.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 6−8 weeks old, 18−21 g, LPS-induced)[1]
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Dosage:25 mg/kg; 50 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 16 days
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Result:Significantly reduced LPS-induced kidney and spleen indices, with the 100 mg/kg dose showing the strongest effect.
Improved renal function, reducing serum creatinine and urea nitrogen levels; the 50 and 100 mg/kg doses showed greater improvement than the positive control dexamethasone.
Mitigated LPS-induced kidney pathological changes (tubular dilation, brush border necrosis, vacuolization, structural disruption) and spleen pathological changes (nuclear swelling, cellular edema, inflammatory infiltration, microcirculatory dysfunction).
Significantly reduced serum levels of pro-inflammatory cytokines TNF-α, IL-6, MCP-1, and IL-1β, with the 100 mg/kg dose showing the strongest suppression.
Significantly suppressed p-eIF4E expression and downregulated the M1 macrophage marker iNOS in kidney and spleen tissues, with the 100 mg/kg dose showing the strongest effect.
Restored antioxidant capacity by increasing glutathione and superoxide dismutase levels, and reduced lipid peroxidation by lowering malondialdehyde levels in tissues.
- Kinase activity and phosphorylation assays
- Phagocytosis Functional Assay
- Western Blot
- LPS-Induced Endotoxemia/Systemic Inflammation
- ROS/oxidative-stress fluorescent staining
- Carrageenan-Induced Paw Edema
- Zymosan-Induced Peritonitis
- Primary monocyte-to-macrophage differentiation
- Protocol for Kinase activity and phosphorylation assays
- Research Protocol for Inflammation-related Diseases
Chemical Information
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Masse moléculaire 520.63
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Formule C25H24N6O3S2
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SMILES
O=C(N1CCN(S(CCC)(=O)=O)CC1)C2=CC=C(C3=NN4C(S3)=NC=C4C5=CC=C(C#N)C=C5)C=C2
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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)
MNK1/2-IN-10 Related Classifications
HY-182939 Related Classifications
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Keywords
- MNK1/2-IN-10
- MNK
- Eukaryotic Initiation Factor (eIF)
- NF-κB
- Mitogen activated protein kinase interacting kinase
- MAP kinase interacting kinase
- MAPK interacting kinase
- Nuclear factor-κB
- Nuclear factor-kappaB
- HUVECs
- oxidative stress
- C57BL/6J mice
- MNK1
- RAW 264.7
- NF-κB signaling
- eIF4E phosphorylation
- MNK2
- macrophage polarization
- HEK293T
- Inhibitor
- inhibitor
- inhibit