EED-IN-5
EED-IN-5 is an orally active, EZH2-selective trisubstituted pyridine-based EED-H3K27me3 inhibitor and immunomodulator with anti-inflammatory activity. The IC50 value of EED-IN-5 against EED is 28.21 nM. In mouse models, EED-IN-5 preferentially and persistently accumulates in lymph nodes after oral administration. By reducing the H3K27me3 level of dendritic cells and inhibiting their migration, EED-IN-5 decreases the infiltration of specific dendritic cells, macrophages and T cells into the spinal cord and brain. EED-IN-5 exhibits hERG inhibitory activity, shows negative results in the Mini-Ames test, and causes no obvious toxicity upon long-term high-dose administration. EED-IN-5 can be used for the research of multiple sclerosis.
For research use only. We do not sell to patients.
- Formula: C23H22FN5O
- Molecular Weight:403.45
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All Histone Methyltransferase Isoforms
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Biological Activity
EED-IN-5 (compound 21) (5 μM; 24 h) reduces the level of H3K27me3 in DC2.4 cells by 60.64% and inhibits CCL19/CCL21-induced cell migration[1].
EED-IN-5 inhibits hERG channel currents in stably transfected HEK293T cells, with an IC50 of 1.2 μM[1].
EED-IN-5 exhibits high selectivity for EED over the methyltransferase activity of EZH2[1].
EED-IN-4 shows negative results in the Mini-Ames mutagenicity assay containing Salmonella typhimurium TA100[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:DC2.4 dendritic cells
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Concentration:5 μM
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Incubation Time:24 h
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Result:Reduced H3K27me3 protein levels in DC2.4 cells by 79.94% compared to control.
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Cell Line:DC2.4 dendritic cells
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Concentration:5 μM
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Incubation Time:24 h (pre-treatment); 12 h (migration assay)
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Result:Suppressed CCL19/CCL21-induced migration of DC2.4 cells by 60.64%, which is 1.6-fold greater efficacy than the positive control EED226.
EED-IN-5 (100 mg/kg; p.o.; twice daily; for consecutive 30 days) shows no obvious acute or subacute toxicity in the C57BL/6 mouse model (equal numbers of male and female mice). The mice exhibit normal weight gain, no significant abnormalities in routine blood test results and liver and kidney function indices, and no histopathological damage to major organs including the heart, liver, spleen, lung, and kidney[1].
EED-IN-5 (80 mg/kg; intragastric administration (i.g.); single dose) preferentially and persistently accumulates in key immune lymph nodes including axillary, inguinal and cervical lymph nodes in healthy female C57BL/6 mice, with a concentration significantly higher than that of EED226, exhibiting favorable lymphoid tissue tropism[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6 mice, 8 weeks old, experimental autoimmune encephalomyelitis (EAE) model[1]
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Dosage:40 mg/kg, 80 mg/kg
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Administration:p.o.; twice daily; from day 9 to day 30 post-immunization
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Result:Dose-dependently reduced disease susceptibility and alleviated clinical symptoms throughout the disease course. It significantly suppressed inflammatory cell infiltration in the spinal cord, decreased the proportions of total CD11c+ DCs, mature DCs (CD11c+CD80+ or CD11c+MHC-II+), F4/80+CD11b+ macrophages, F4/80+CD80+ inflammatory macrophages, and pro-inflammatory Th1 (CD4+IFN-γ+) and Th17 (CD4+IL-17+) T cells in peripheral lymph nodes.
Also reduced the infiltration of CD11c+ DCs, CD11b+ macrophages, and CD4+ T cells into the spinal cord and brain of EAE mice.
Chemical Information
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Molecular Weight 403.45
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Formula C23H22FN5O
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SMILES
N#CC1=CC(NCC2=C(F)C=CC3=C2CCO3)=NC=C1C4=CN=C(CN(C)C)C=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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)