JAK-IN-23 是 JAK/STAT 和 NF-κB 的双重抑制剂，具有口服活性。JAK-IN-23 对J AK1/2/3 具有抑制作用，IC50值分别为 8.9 nM、15 nM 和 46.2 nM。JAK-IN-23 对干扰素刺激基因 (ISG) 和 NF-κB 通路具有较强的抑制活性，IC50值分别为 3.3 nM 和 150.7 nM。JAK-IN-23 具有很强的抗炎作用，可以减少各种促炎因子的释放。JAK-IN-23 可用于炎症性肠病 (IBD) 的研究。
| 生物活性 | JAK-IN-23 is an orally active double inhibitor ofJAK/STAT andNF-κB. JAK-IN-23 can inhibit JAK1/2/3 withIC50values of 8.9 nM, 15 nM and 46.2 nM, respectively. JAK-IN-23 has potent inhibitory activities against interferon-stimulated genes (ISG) andNF-κBpathways withIC50values of 3.3 nM and 150.7 nM, respectively. JAK-IN-23 has great anti-inflammatory that decreases the release of various proinflammatory factors. JAK-IN-23 can be used for the research of inflammatory bowel disease (IBD)[1]. |
| IC50& Target[1] | JAK1 8.9 nM (IC50) | JAK2 15 nM (IC50) | JAK3 46.2 nM (IC50) | NF-κB 150.7 nM (IC50) | ISG 3.3 nM (IC50) |
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体外研究
(In Vitro) | JAK-IN-23 inhibits JAK1/2/3 with IC50values of 8.9 nM, 15 nM and 46.2 nM, respectively[1].
JAK-IN-23 shows potent inhibitory activities against ISG and NF-KB with IC50values of 3.3 nM and 150.7 nM, respectively[1].
WB--- JAK-IN-23 (0.33μM, 1μM, 3μM; 24 h) can simultaneously block JAK-STAT1/3 and NF-κB proinflammatory signaling pathways in THP1-dual cells[1].
JAK-IN-23 (0.003-3 μM; 24 h) decreases the release of various proinflammatory factors, including IL-6, IL-8, IL-1β in THP1-dual cells stimulated by LPS[1].
JAK-IN-23 (0.11-3 μM; 24 h) decreases the release of various proinflammatory factors, including TNF-α, IL-12, IL-10 and IFNγ in LPS-induced peripheral blood mononuclear cells (PBMCs)[1].
JAK-IN-23 (1 μM) inhibits the expression of a variety of inflammation-related genes induced by LPS, including IL-1B, TNF, IL12B, and IL-23A and has inhibitory effects on the expression of genes involved in the unfolded protein response that was induced by LPS (1 μg/mL)[1].
Western Blot Analysis[1] | Cell Line: | THP1-Dual Cells | | Concentration: | 0.33μM, 1μM, 3μM | | Incubation Time: | 24 h | | Result: | Inhibited p-STAT1/3 in a dose-dependent manner that was induced by IL-6, as well as inhibited pNF-κB p65 in a dose-dependent manner, but not on MYD88 and p-IKK α/β that was induced by LPS. |
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体内研究
(In Vivo) | JAK-IN-23 (1-5 mg/kg, oral) produces a strong anti-inflammatory activity in both dextran sulfate sodium (DSS) - and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute enteritis models and restores the structural composition of gut microbiota[1].
| Animal Model: | DSS-Induced Acute Colitis Mice Model[1] | | Dosage: | 1 mg/kg, 3 mg/kg | | Administration: | oral | | Result: | Significantly decreased the DAI scores (1 and 3 mg/kg).
Recovered the length of the colon (3 mg/kg).
Significantly reduced the histopathology of ulcerative colitis (1 and 3 mg/kg). |
| Animal Model: | The BALB/c mouse inflammatory bowel disease (IBD) model[1] | | Dosage: | 1 mg/kg, 5 mg/kg | | Administration: | oral | | Result: | Significantly improved the survival probability, had low DAI scores and effectively relieved symptoms of colitis in the TNBS-induced IBD mice model (5 mg/kg).
Did not improve the survival probability and decreases the DAI score (100 mg/kg). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 5 mg/mL(11.33 mM;ultrasonic and warming and heat to 80℃) 配制储备液 | 1 mM | 2.2658 mL | 11.3289 mL | 22.6578 mL | | 5 mM | 0.4532 mL | 2.2658 mL | 4.5316 mL | | 10 mM | 0.2266 mL | 1.1329 mL | 2.2658 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
