受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | JNK Inhibitor XVI | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C29H29N7O2 |
|||
分子量 | 507.59 | CAS No. | 1410880-22-6 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL warmed with 50ºC water bath (197.0 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | JNK-IN-8 (JNK Inhibitor XVI) is the first irreversible JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 4.7 nM, 18.7 nM and 1 nM, >10-fold selectivity against MNK2, Fms and no inhibition to c-Kit, Met, PDGFRβin A375 cell line. |
---|---|
in vitro | 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. [1] 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. [2] 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. [3] |
in vivo | JNK-IN-8 is a potent JNK inhibitor that specially targets JNK activation. It has anti-fungal activity. |
特徴 | JNK-IN-8 and JNK-IN-7 are structurally very similar, but whereas the former is a specific covalent inhibitor of JNKs. |
キナーゼアッセイ | Binding Kinetics Assay | |
---|---|---|
Binding kinetics assay A375 cells are pretreated with 1 μM JNK-IN-8 for the indicated amounts of time. Remove the medium and wash three times with PBS. Resuspend the cell pellet with 1 mL Lysis Buffer (1% NP-40, 1% CHAPS, 25 mM Tris, 150 mM NaCl, Phosphatase Inhibitor Cocktail, and Protease Inhibitor Cocktail). Rotate end to end for 30 min at 4℃. Lysates are cleared by centrifugation at 1.4×104 rpm for 15 min in the Eppendorf. The cleared lysates are gel filtered into Kinase Buffer (0.1% NP-40, 20 mM HEPES, 150 mM NaCl, Phosphatase Inhibitor Cocktail, Protease Inhibitor Cocktail) using 10DG columns. The total protein concentration of the gel-filtered lysate should be around 5–15 mg/ml. Cell lysate is labeled with the probe from ActivX at 5 μM for 1 hour. Samples are reduced with DTT, and cysteines are blocked with iodoacetamide and gel filtered to remove excess reagents and exchange the buffer. Add 1 vol of 2× Binding Buffer (2% Triton-100, 1% NP-40, 2 mM EDTA, 2× PBS) and 50 μL streptavidin bead slurry, and rotate end to end for 2 hours, centrifuge at 7,000 rpm for 2 min. Wash three times with 1× Binding Buffer and three times with PBS. Add 30 μL 1× sample buffer to beads; heat samples at 95℃ for 10 min. Run samples on an SDS-PAGE gel at 110V. After transferred, the membrane is immunoblotted with JNK antibody. | ||
細胞アッセイ | 細胞株 | A375 cells |
濃度 | 4.7, 18.7 & 1 nM (JNK1, 2, & 3, respectively) | |
反応時間 | ||
実験の流れ | Cells were treated with various concentrations of JNK-IN-8. |
|
動物実験 | 動物モデル | C57BL/6 mice |
投薬量 | 10 mg/kg | |
投与方法 | i.p. |
Data from [Biochem Biophys Res Commun, 2013, 440(4), 701-6]
Data from [Data independently produced by , , J Exp Med, 2015, 212(5): 775-92]
Data from [Data independently produced by , , Neurobiol Dis, 2018, 110:37-46]
Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer [ Cancer Cell, 2024, 42(4):535-551.e8] | PubMed: 38593780 |
Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways [ Mil Med Res, 2023, 10(1):56] | PubMed: 38001521 |
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] | PubMed: 37462944 |
Chemical-induced epigenome resetting for regeneration program activation in human cells [ Cell Rep, 2023, 42(6):112547] | PubMed: 37224020 |
Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors [ Sci Signal, 2023, 16(767):eabm5518] | PubMed: 36626580 |
Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors [ Sci Signal, 2023, 16(767):eabm5518] | PubMed: 36626580 |
Phosphorylation-Assisted Luciferase Complementation Assay Designed to Monitor Kinase Activity and Kinase-Domain-Mediated Protein-Protein Binding [ Int J Mol Sci, 2023, 24(19)14854] | PubMed: 37834301 |
An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression [ Int J Mol Sci, 2023, 24(4)3968] | PubMed: 36835391 |
p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis [ J Biol Chem, 2023, 299(4):103043] | PubMed: 36803959 |
Identification of Kinase Targets for Enhancing the Antitumor Activity of Eribulin in Triple-Negative Breast Cell Lines [ Biomedicines, 2023, 11(3)735] | PubMed: 36979714 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。