JNK-IN-8
(Synonyms: JNK Inhibitor XVI) 目录号 : GC13841
JNK-IN-8 是第一个不可逆的JNK抑制剂,作用于JNK1,JNK2和JNK3,具有高度特异性,在A375细胞系中IC50分别为4.7 nM,18.7 nM和1 nM。
Cas No.:1410880-22-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HEK293-ILR1、A375 cells |
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Preparation Method |
The cells were incubated with JNK-IN-8 at concentrations of 0.1, 0.3, 1, and 3 µM for 3 h. |
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Reaction Conditions |
0.1, 0.3, 1, 3 µM ; 3 h |
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Applications |
The superior potency and selectivity of JNK-IN-8 in the HEK293 cells suggested that the compound would likely serve as very useful pharmacological probes of JNK-dependent cellular phenomena. |
| Animal experiment [2]: | |
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Animal models |
SD rats |
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Preparation Method |
Rats were given an intraperitoneal injection of vehicle (saline 150 δl and 20% dimethylsulfoxide in PBS) or JNK-IN-8 (20 mg/kg dissolved in 20% dimethylsulfoxide) after MCAO. |
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Dosage form |
20 mg/kg; i.p. |
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Applications |
JNK-IN-8-treated rats with MCAO exerted a significant improvement in spatial learning as measured by the improved mNSS, and showed sensorimotor functional recovery as measured by the Foot-fault test. |
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References: [1]Zhang T, Inesta-Vaquera F, et al, Discovery of potent and selective covalent inhibitors of JNK. Chemical Biology. 2012, 19(1):140-154. |
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JNK-IN-8 is the first irreversible JNK inhibitor that acts on JNK1, JNK2, and JNK3 with high specificity, with IC50 values of 4.7 nM, 18.7 nM, and 1 nM in the A375 cell line, respectively[1]. JNK-IN-8 forms a covalent bond with the conserved cysteine residue of JNK 1/2/3, causing a conformational change in the activation loop and blocking substrate binding, thereby inhibiting the activity of JNK 1/2/3[1]. JNK 1, 2, and 3 are part of the mitogen-activated protein kinase (MAPK) family, capable of phosphorylating the Ser 63 and Ser 73 residues of c-Jun, responding to stress stimuli such as cytokines and heat shock, and involved in T cell differentiation and apoptosis processes.
In vitro, JNK-IN-8 inhibits c-Jun phosphorylation in HeLa and A375 cells, with EC50 values of 486 nM and 338 nM, respectively[1]. JNK-IN-8 also shows significant selectivity in HEK 293 cells[1]. Additionally, JNK-IN-8 (10 mM) exhibits anti-inflammatory effects, reducing microglial activation and the expression of IL-6, IL-1β, and TNF-α[2].
In vivo, JNK-IN-8 (20 mg/kg; i.p.) treated rats with middle cerebral artery occlusion show significant improvements in spatial learning and sensorimotor function recovery[2]. Administration of JNK-IN-8 (3µg/µL) into the lateral ventricles of male KM mice 24 h before brain injury significantly reduces neuronal apoptosis after brain injury[3].
References:
[1] Zhang T, Inesta-Vaquera F, et al, Discovery of potent and selective covalent inhibitors of JNK. Chemical Biology. 2012, 19(1):140-154.
[2] Geng W , Tang H , Dai Q ,et al. JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke[J].Cold Spring Harbor Laboratory, 2018.
[3] Li D1, Liu N, 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.
JNK-IN-8 是第一个不可逆的JNK抑制剂,作用于JNK1,JNK2和JNK3,具有高度特异性,在A375细胞系中IC50分别为4.7 nM,18.7 nM和1 nM[1]。JNK-IN-8与JNK 1/2/3的保守半胱氨酸残基形成共价键,导致激活环的构象变化,阻断底物结合,从而抑制JNK 1/2/3的活性[1]。JNK 1、2和3属于丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)家族,能够磷酸化c-Jun的Ser 63和Ser 73残基,对细胞因子和热休克等应激刺激有应答,参与T细胞分化和细胞凋亡过程。
在体外,JNK-IN-8 抑制 HeLa和A375细胞中的c-Jun磷酸化,EC50分别为 486 nM和338 nM[1]。JNK-IN-8在HEK 293细胞中还表现出显著的选择性[1]。JNK-IN-8 (10 mM)还发挥抗炎作用,使小胶质细胞活化减少以及 IL-6、IL-1β和TNF-α 表达减少[2]。
在体内,JNK-IN-8 (20 mg/kg; i.p.)治疗的大脑中动脉闭塞大鼠在空间学习方面表现出显着改善,并且感觉运动功能恢复[2]。JNK-IN-8在雄性KM小鼠脑损伤前24 h向侧脑室注射3µg/µL 能显著减少脑损伤后神经元凋亡[3]。
| Cas No. | 1410880-22-6 | SDF | |
| 别名 | JNK Inhibitor XVI | ||
| 化学名 | 3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-methyl-4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide | ||
| Canonical SMILES | CC1=C(C=CC(=C1)NC(=O)C2=CC(=CC=C2)NC(=O)C=CCN(C)C)NC3=NC=CC(=N3)C4=CN=CC=C4 | ||
| 分子式 | C29H29N7O2 | 分子量 | 507.59 |
| 溶解度 | ≥ 25.4 mg/mL in DMSO, ≥ 9.24 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9701 mL | 9.8505 mL | 19.7009 mL |
| 5 mM | 0.394 mL | 1.9701 mL | 3.9402 mL |
| 10 mM | 0.197 mL | 0.985 mL | 1.9701 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。