JNK-IN-8

製品コードS4901 バッチS490102

印刷

化学情報

Chemical Structure 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.

溶剤液（一定の濃度）を調合する

生物活性

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.

プロトコル(参考用のみ)

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.

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

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