1410880-22-6

Basic information

• Product Name: JNK-IN-8
• Synonyms: JNK-IN-8;(E)-3-(4-(diMethylaMino)but-2-enaMido)-N-(3-Methyl-4-(4-(pyridin-3-yl)pyriMidin-2-ylaMino)phenyl)benzaMide;3-[[4-(Dimethylamino)-1-oxo-2-buten-1-yl]amino]-N-[3-methyl-4-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide;JNK Inhibitor XVI;Benzamide, 3-[[4-(dimethylamino)-1-oxo-2-buten-1-yl]amino]-N-[3-methyl-4-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-;3-[[4-(Dimethylamino)-1-oxo-2-buten-1-yl]amino]-N-[3-methyl-4-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide JNK-IN-8
• CAS NO: 1410880-22-6
• Molecular Formula: C29H29N7O2
• Molecular Weight: 507.58626
• Product Categories: MAPK;Inhibitors
• Mol File: 1410880-22-6.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.283±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: ≥25.4 mg/mL in DMSO; insoluble in H2O; ≥9.24 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 13.34±0.70(Predicted)
• CAS DataBase Reference: JNK-IN-8(CAS DataBase Reference)
• NIST Chemistry Reference: JNK-IN-8(1410880-22-6)
• EPA Substance Registry System: JNK-IN-8(1410880-22-6)

Safety Data

• Hazardous Substances Data: 1410880-22-6(Hazardous Substances Data)

Usage

Uses

JNK-IN-8 has been used as an inhibitor to address the importance of JNK signaling in withaferin A (WFA)-induced apoptosis of myelodysplastic syndromes (MDS)-L cells.

Biological Activity

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].

Biochem/physiol Actions

JNK-IN-8 is a potent, selective and irreversible inhibitor of JNK1/2/3 that inhibits phosphorylation of c-Jun. JNK-IN-8 forms covalent bonds with a conserved cysteine residue.

references

[1]. zhang t et al., discovery of potent and selective covalent inhibitors of jnk. chemical biology. 2012, 19(1):140-154.

Relevant articles and documents

INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK)

The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L1, L2, RA, RC, RD, RE, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.