EED-IN-4
EED-IN-4 is an orally active, EZH2-selective immunomodulator and EED-H3K27me3 inhibitor (EED, IC50=28.21 nM) with anti-inflammatory activity. In mouse models, EED-IN-4 preferentially and persistently accumulates in lymph nodes after oral administration. By reducing the H3K27me3 level of dendritic cells and inhibiting their migration, EED-IN-4 reduces the infiltration of immune cells into the central nervous system and effectively alleviates spinal cord inflammation. EED-IN-4 shows weak inhibitory activity against hERG channels and is non-mutagenic, with no obvious toxicity observed upon long-term oral administration. EED-IN-4 can be used for the research of multiple sclerosis.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C22H20FN5O
- 分子量:389.43
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
EED-IN-4 (compound 19) (5 μM; 24 h) reduces the level of H3K27me3 in DC2.4 cells by 79.94% and inhibits cell migration induced by CCL19/CCL21[1].
EED-IN-4 only weakly inhibits hERG channel currents in stably transfected HEK293T cells, with an IC50 >10 μM[1].
EED-IN-4 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.
| Species | Dose | Route | Tmax | T1/2 | Cmax | AUC0-t | AUC0-∞ |
|---|---|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | i.g. | 1.00 h | 2.74 h | 495.43 ng/mL | 3951.73 ng·h/mL | 3964.15 ng·h/mL |
EED-IN-4 (100 mg/kg; p.o.; twice daily; for consecutive 30 days) shows no obvious acute or subacute toxicity in the C57BL/6 mouse model (with equal numbers of male and female mice). The mice exhibit normal body weight gain, no significant abnormalities in blood routine, liver and kidney function indices, and no histopathological damage in major organs including the heart, liver, spleen, lung and kidney[1].
EED-IN-4 (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.
化学情報
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分子量 389.43
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分子式 C22H20FN5O
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SMILES
CN(C)C1=CC=C(C2=CN=C(NCC3=C(F)C=CC4=C3CCO4)C=C2C#N)C=N1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)