2409109-65-3
2409109-65-3 structure
- Name: JNK3 inhibitor-4
- Chemical Name: JNK3 inhibitor-4
- CAS Number: 2409109-65-3
- Molecular Formula: C28H27N7O
- Molecular Weight: 477.56
- Catalog: Signaling Pathways MAPK/ERK Pathway JNK
- Create Date: 2023-01-08 20:28:22
- Modify Date: 2024-04-13 23:35:02
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JNK3 inhibitor-4 is a potent inhibitor of JNK3 (IC50=1.0 nM) based on 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile. JNK3 inhibitor-4 shows excellent selectivity over other protein kinases including isoforms JNK1 (IC50=143.9 nM) and JNK2 (IC50=298.2 nM)[1]. JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability[1].
| Name | JNK3 inhibitor-4 |
|---|
| Description | JNK3 inhibitor-4 is a potent inhibitor of JNK3 (IC50=1.0 nM) based on 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile. JNK3 inhibitor-4 shows excellent selectivity over other protein kinases including isoforms JNK1 (IC50=143.9 nM) and JNK2 (IC50=298.2 nM)[1]. JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability[1]. |
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| Related Catalog | |
| Target |
JNK3:1.0 nM (IC50) JNK1:143.9 nM (IC50) JNK2:298.2 nM (IC50) |
| In Vitro | JNK3 inhibitor-4 (化合物 15d) (1,5,10,20 μM; 24 h 或 48 h) 抑制 Aβ1-42 诱导的对大鼠原代皮层神经元的细胞毒性[1]。 JNK3 inhibitor-4 (10, 20 μM; 24 h、48 h) 抑制 10 μM Aβ1-42 或 0.5 μM Anisomycin (HY-18982) 诱导的大鼠皮层神经元 c-jun 磷酸化和 APP 磷酸化[1]。 JNK3 inhibitor-4 (50 μM; 4 h) 在 Caco-2 试验中具有高渗透性，根据 PAMPA 试验中的有效渗透系数 (Pe) > 4，预测其具有血脑屏障 (CNS+) 渗透性[1]。 JNK3 inhibitor-4 也抑制 GSK3α (h)、GSK3β (h)、JNK1、2、MKK6、MOK、SAPK2a (h)、SAPK2a (T106 M) (h)、SAPK2b (h)、MKK4、JNK1α1 (h) 和JNK2α1 (h)，其 IC50 值分别为 5.78、11.7、15.1、1.18、3.10、1.19、0.280、0.970、0.860 和 0.340 μM[1]。 Western Blot Analysis[1] Cell Line: Primary rat cortex neuron Concentration: 10 μM and 20 μM Incubation Time: 24 hours Result: Monomeric Aβ1-42 induced c-jun phosphorylation dose-dependently and that was inhibited by JNK3 inhibitor-4 in concentration-dependent manner. Cell Viability Assay[1] Cell Line: Primary rat cortex neuron Concentration: 1, 5, 10, 20 μM Incubation Time: 24 hours and 48 hours Result: Showed neuroprotective effect and increased cell viability under Aβ1-42 treatment. |
| In Vivo | JNK3 inhibitor-4 (化合物 15d) 能够改善阿尔茨海默病模型小鼠的记忆力。JNK3 inhibitor-4 (10 mg/kg 或 30 mg/kg; 静脉注射; 每周 3 次，共 1 个月) 在 Y 迷宫试验和被动回避试验中，与 APP/PS1 载药组相比，显著改善了小鼠的自发改变和反应延迟行为 (第 27 天或第 30 天)，并表现出剂量相关性[1]。 JNK3 inhibitor-4 (30 mg/kg; 静脉注射; 单剂量; 记录 0-6 h) 在 SD 大鼠中显示血脑屏障通透性，脑/血浆浓度比为 0.02 (26 ng/g vs 1084 ng/mL)[1]。 Pharmacokinetics in rats[1] Route Dose (mg/kg) AUC0-t (ng·h/mL) Cmax (ng/mL) Tmax (h) T1/2 (h) BA (%) IV 1 718.0 0.22 PO 3 337.5 377.82 0.63 0.34 15.67 |
| References |
| Molecular Formula | C28H27N7O |
|---|---|
| Molecular Weight | 477.56 |