切换导航

JNK-IN-8

现货
Catalog No.
A3520
JNK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,520.00
现货
5mg
¥ 1,200.00
现货
10mg
¥ 1,800.00
现货
50mg
¥ 5,400.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

JNK-IN-8 is a specific JNK1/2/3 inhibitor with IC50 value of 4.67, 18.7, 0.98 nM respectively [1].

C-Jun N-terminal kinase (JNK) 1, 2 and 3 belong to the mitogen-activated protein kinase (MAPK) family, which are able to phosphorylate c-Jun on the Ser63 and Ser73 residue.They are responsive for stress stimuli, including cytokines and heat shock, and get involved in T cell differentiation and cell apoptosis process. JNK 1 and 2 are ubiquitous in all cell types but JNK 3 is only found in cells of brain, heart and testes tissues.

JNK-IN-8 is a JNK1/2/3 inhibitor with high specificity. When JNK-IN-8 was profiled with a panel of 400 kinases, it exhibited specific binding to JNK 1/2/3 but not to other kinases. Crystallization study also found that JNK-IN-8 forms covalent bonds with conserved cysteine residue of JNK 1/2/3, resulting in a conformational change of the activation loop that blocks the substrate binding, thereby inhibiting the activity of JNK 1/2/3 [1].

In Hela cells and A375 cells, pretreatment of cells with JNK-IN-8 resulted in the inhibition of c-Jun which is a direct phosphorylation substrate of JNK 1/2/3, confirming the inhibitory action of JNK-IN-8 on JNK 1/2/3. In HEK293-ILR1 cells following stimulation by anisomycin, the JNK-IN-8 was observed to inhibit c-Jun but not MSK1 and p38, and the inhibition was not reversible by removing JNK-IN-8 from culture medium. Additionally, JNK-IN-8 only exhibited on-pathway inhibition of JNK signaling pathway, which can be monitored by the phosphorylation of c-Jun [1].

Reference:
[1].  Zhang T et al., Discovery of potent and selective covalent inhibitors of JNK. Chemical Biology. 2012, 19(1):140-154.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt507.59
Cas No.1410880-22-6
FormulaC29H29N7O2
Solubility≥25.4 mg/mL in DMSO, ≥9.24 mg/mL in EtOH with ultrasonic and warming, <2.61 mg/mL in H2O
Chemical Name3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-methyl-4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
SDFDownload SDF
Canonical SMILESCC1=C(C=CC(=C1)NC(=O)C2=CC(=CC=C2)NC(=O)C=CCN(C)C)NC3=NC=CC(=N3)C4=CN=CC=C4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HEK293-ILR1细胞

溶解方法

在DMSO中的溶解度>25.4mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月

反应时间

0.1,0.3,1,3μM,3hr

应用

JNK-IN-8是酶的和细胞的JNK(C-Jun N端激酶)的强效的抑制剂,它可以抑制JNK的直接底物c-Jun的磷酸化。由于JNK-IN-8在HEK293细胞中表现出的出色的效能和选择性,它被认为可以作为一个有用的JNK依赖的细胞现象的药理学探针。

动物实验[2]:

动物模型

雄性KM小鼠(清洁级)(8周龄)

剂量

3μg/μL,注射

应用

JNK-IN-8是一个JNK路径的特异性的抑制剂,它在脑损伤后相比于DMSO对照组可以显著的减少神经元的凋亡

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Zhang T1, Inesta-Vaquera F, et al, Discovery of potent and selective covalent inhibitors of JNK. Chemical Biology. 2012, 19(1):140-154.

[2]. Li D1, Liu N1,et al, Protective effect of resveratrol against nigrostriatal pathway injury in striatum via JNK pathway. Brain Res. 2017 Jan 1;1654(Pt A):1-8. doi: 10.1016/j.brainres.2016.10.013. Epub 2016 Oct 18.

生物活性

描述 JNK-IN-8是一种选择性的和不可逆的II型JNK抑制剂,作用于JNK1、JNK2 和JNK3,IC50值分别为4.67 nM、18.7 nM和980 pM。
靶点 JNK1 JNK2 JNK3      
IC50 4.67 nM 18.7 nM 980 pM      

质量控制