JNK Inhibitor VIII

Catalog No.S7794 Batch:S779401

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Technical Data

Formula

C18H20N4O4
Molecular Weight 356.38 CAS No. 894804-07-0
Solubility (25°C)* In vitro DMSO 71 mg/mL (199.22 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.55mg/ml
5% DMSO 95% Corn oil
1.7mg/ml
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description JNK Inhibitor VIII (TCS JNK 6o) is an inhibitor of c-Jun N-terminal kinases with IC50 of 45 nM and 160 nM for JNK-1 and JNK-2, respectively. JNK Inhibitor VIII (TCS JNK 6o) inihibits JNK-1, JNK-2, and JNK-3 with Ki of 2 nM, 4 nM and 52 nM, respectively.
Targets
JNK1 [1]
(Cell-free assay)		 JNK2 [1]
(Cell-free assay)		 JNK1 [1]
(Cell-free assay)		 JNK3 [1]
(Cell-free assay)		 JNK2 [1]
(Cell-free assay)
2 nM(Ki) 4 nM(Ki) 45 nM 52 nM(Ki) 160 nM
In vitro

TCS-JNK-6a binds competitively and reversibly to the ATP site. This compound demonstrates a remarkable selectivity profile. Additionally, it shows some inhibition of c-Jun phosphorylation in hepG2 cells. TCS-JNK-6o is a 2,5-dimethoxy analogue of TCS-JNK-6a with the dimethoxy substitution of the phenyl ring. TCS-JNK-6o shows further gains in potency.[1]
In vivo

Pharmacokinetic profiles are determined for JNK Inhibitor VIII (TCS-JNK-6o) in Sprague-Dawley rats. JNK Inhibitor VIII (TCS-JNK-6o) showes a short half-life of roughly 1 h, with rapid clearance and barely measurable bioavailability. Microsomal incubation studies revealed that oxidative metabolism is very rapid with this compound.[1]

Protocol (from reference)

Kinase Assay:

[1]
  • Ser/Thr-kinase

    Ser/Thr-kinase assays are performed using a radioactive FlashPlate-based assay platform. In this format, biotinylated substrate peptide (2 μM), γ-[33P]-ATP (5 μM, 2 mCi/μmol), inhibitors (3-10000 nM in 2% DMSO), and enzyme are incubated for 1 h in buffer containing 25 mM Hepes, pH 7.5, 1 mM DTT, 10 mM MgCl2, 100 μM Na3VO4, and 0.075 mg/mL Triton X-100, stopped with 80 μL of stop buffer containing 100 mM EDTA and 4 M NaCl, transferred to streptavidin-coated 384-well FlashPlates, which are then washed 3 times and read using a TopCount microplate reader.
Cell Assay:

[1]
  • Cell lines

    hepG2 cells

  • Concentrations

    Serial concentrations

  • Incubation Time

    1 h

  • Method

    HepG2 human hepatoma cells (ATCC) are cultured in low glucose MEM supplemented with 1×NEAA, 1×sodium pyruvate, and 10% FBS. For P-c-Jun assays, cells are plated at 5×104 cells/well in 500 μL of complete media on 24-well collagen-coated plates and incubated overnight. Serial compound dilutions are made in DMSO at 100×, and then 5 μL is added directly to the media on the cells to provide the final inhibitor concentrations. After 1 h, cells are stimulated with vehicle control or TNFR for 30 min and harvested in 70μL of lysis buffer (TBS (54 mM Tris-HCl, pH 7.6, 150 mM NaCl), 1% TritonX-100,0.5% Nonidet P-40, 0.25% sodium deoxycholate, 1 mM EDTA, 1 mM EGTA, 0.5 mM sodium fluoride, 1 mM pervanadate, 1 μM microcystin, 1 mM AEBSF, 1 tablet of complete EDTA Free-Mini inhibitor cocktail) and frozen at -80 °C prior to use in the P-c-Jun assay.
Animal Study:

[1]
  • Animal Models

    Sprague-Dawley rat

  • Dosages

    5 mg/kg

  • Administration

    IV, Oral gavage

Selleck's JNK Inhibitor VIII has been cited by 4 publications

Blocking GSDME-mediated pyroptosis in renal tubular epithelial cells alleviates disease activity in lupus mice [ Cell Death Discov, 2022, 8(1):113] PubMed: 35279675
Dabrafenib Promotes Schwann Cell Differentiation by Inhibition of the MEK-ERK Pathway [ Molecules, 2021, 26(8)2141] PubMed: 33917810
Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection [ PLoS Pathog, 2018, 14(11):e1007418] PubMed: 30496310
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells [ PLoS One, 2015, 10(11):e0143685] PubMed: 26606677

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.