| CAS NO: | 1410880-22-6 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 507.59 |
|---|---|
| Formula | C29H29N7O2 |
| CAS No. | 1410880-22-6 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 100 mg/mL (197.0 mM) |
| Water: <1 mg/mL | |
| Ethanol:<1 mg/mL | |
| Solubility (In vivo) | 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 10mg/mL |
| Synonyms | Synonym: JNK Inhibitor XVI; JNK-IN 8; JNK-IN8; JNK-IN 8; c-Jun N-terminal Kinase Inhibitor XVI. Chemical Name: (E)-3-(4-(dimethylamino)but-2-enamido)-N-(3-methyl-4-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide InChi Key: GJFCSAPFHAXMSF-UXBLZVDNSA-N InChi Code: InChI=1S/C29H29N7O2/c1-20-17-24(11-12-25(20)34-29-31-15-13-26(35-29)22-8-5-14-30-19-22)33-28(38)21-7-4-9-23(18-21)32-27(37)10-6-16-36(2)3/h4-15,17-19H,16H2,1-3H3,(H,32,37)(H,33,38)(H,31,34,35)/b10-6+ SMILES Code: CN(C/C=C/C(NC1=CC=CC(C(NC2=CC=C(C(C)=C2)NC3=NC=CC(C4=CN=CC=C4)=N3)=O)=C1)=O)C |
| In Vitro | In vitro activity: JNK-IN-8 inhibits c-Jun phosphorylation in HeLa and A375 cells with EC50 of 486 nM and 338 nM, respectively. JNK-IN-8 shows a dramatic improvement in selectivity and eliminated binding to IRAK1, PIK3C3, PIP4K2C, and PIP5K3. JNK-IN-8 requires Cys116 for JNK2 inhibition. JNK-IN-8 (10 mM) suppresses the IL-1β-stimulated phosphorylation of c-Jun in IL-1R cells, an established substrate of the JNKs. JNK-IN-8 covalently attaches to the JNK isoforms caused a small retardation in the electrophoretic mobility of the JNK isoforms. JNK-IN-8 is discovered to inhibit JNK kinase by broad-based kinase selectivity profiling of a library of acrylamide kinase inhibitors based on the structure of imatinib using the KinomeScan approach. JNK-IN-8 possesses distinct regiochemistry of the 1,4-dianiline and 1,3-aminobenzoic acid substructures relative to imatinib and uses an N,N-dimethyl butenoic acetamide warhead to covalently target Cys154. JNK-IN-8 adopts an L-shaped type I binding conformation to access Cys 154 located toward the lip of the ATP-binding site Kinase Assay: 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. Cell Assay: 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. |
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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Chem Biol. 2012 Jan 27;19(1):140-54; Biochem J. 2012 Jan 1;441(1):339-46; Chem Biol. 2013 Feb 21;20(2):146-59. |
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