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JNK3 inhibitor-4

CAS No. : 2409109-65-3

MCE 站：JNK3 inhibitor-4

产品活性：JNK3 inhibitor-4 是一种强效 JNK3 抑制剂 (IC₅₀=1.0 nM)，是基于 2-芳基-1-嘧啶基-1H-咪唑-5-基乙腈的化合物。JNK3 inhibitor-4 对其他蛋白激酶具有极好的选择性，包括同种型 JNK1 (IC₅₀=143.9 nM) 和 JNK2 (IC₅₀=298.2 nM)。JNK3 inhibitor-4 具有神经保护作用和预测的血脑屏障通透性。

研究领域：MAPK/ERK Pathway

作用靶点：JNK

In Vitro: JNK3 inhibitor-4 (compound 15d) (1, 5, 10, 20 μM; 24 h ａnd 48 h) inhibits Aβ_1-42 induced Aβ1-42-induced cellular toxicity in primary rat cortex neuron.
JNK3 inhibitor-4 (10 μM ａnd 20 μM; 24 h ａnd 48 h) inhibits c-jun phosphorylation ａnd APP phosphorylation induced by 10 μM Aβ_1-42 or 0.5 μM Anisomycin (HY-18982) in primary rat cortex neuron.
JNK3 inhibitor-4 (50 μM; 4 h) shows high permeability in Caco-2 assay ａnd is predicted as BBB permeable (CNS+) based on effective permeability coefficient (Pe) value > 4 in PAMPA assay.
JNK3 inhibitor-4 also shows inhibitory potency on GSK3α (h), GSK3β (h), JNK1, 2, MKK6, MOK, SAPK2a (h), SAPK2a (T106 M) (h), SAPK2b (h), MKK4, JNK1α1 (h), ａnd JNK2α1 (h). These shows IC₅₀ values of 5.78, 11.7, 15.1, 1.18, 3.10, 1.19, 0.280, 0.970, 0.860, ａnd 0.340 μM, respectively.

In Vivo: JNK3 inhibitor-4 improves memory for the Alzheimer’s disease mouse model. JNK3 inhibitor-4 (compound 15d) (10 or 30 mg/kg; i.v.; 3 times/week for 1 month in 9-month-old APP/PS1 3Tx3Tg mice) results significantly higher spontaneous alteration ａnd response latency of mouse (at 27th or 30th days) compared to the APP/PS1vehicle groups in Y-maze test ａnd passive avoidance test, with a dose correlation.
JNK3 inhibitor-4 (30 mg/kg; p.o.; single dose) shows blood-brain barrier permeability with brain to plasma ratio of 0.02 in SD rats.
Pharmacokinetics in rats

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