| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
JNK1 (Ki = 2 nM); JNK1 (IC50 = 45 nM); JNK2 (Ki = 4 nM); JNK2 (Ki = 160 nM); JNK3 (Ki = 52 nM)
JNK Inhibitor VIII targets JNK-1, JNK-2, and JNK-3, which are key components of the MAPK signaling pathway. By competitively binding to the ATP site, it inhibits the phosphorylation of c-Jun and other transcription factors, thereby modulating cellular processes such as apoptosis, inflammation, and cell proliferation. It inhibits c-jun phosphorylation with an EC50 of 920 nM in HepG2 cells. |
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| ln Vitro |
TCS-JNK-6a binds to the ATP site in a competitive and reversible manner. This substance exhibits an impressive selectivity profile. In hepG2 cells, it also exhibits some inhibition of c-Jun phosphorylation. TCS-JNK-6o is a 2,5-dimethoxy analogue of TCS-JNK-6a in which the phenyl ring has been replaced by a dimethoxy group. TCS-JNK-6o exhibits additional increases in potency. [1]
In vitro, JNK Inhibitor VIII demonstrates potent inhibitory activity against JNK kinases. It has Ki values of 2.0 nM, 4.0 nM, and 52.0 nM for JNK1, JNK2, and JNK3, respectively. It inhibits JNK-mediated ATF2 phosphorylation. It shows some inhibition of c-Jun phosphorylation in HepG2 cells. It preferentially blocks the growth of PTEN null mouse embryonic fibroblasts. |
| ln Vivo |
JNK Inhibitor VIII (TCS-JNK-6o) pharmacokinetic profiles are established in Sprague-Dawley rats. The JNK Inhibitor VIII (TCS-JNK-6o) exhibits a brief half-life of about 1 h, rapid clearance, and hardly detectable bioavailability. Studies on microsomal incubation have shown that this compound has a very quick oxidative metabolism. [1]
In vivo, JNK Inhibitor VIII is used as a research tool to study the role of JNK signaling in various physiological and pathological processes. By inhibiting JNK, it can modulate apoptosis, inflammation, and cell proliferation. It is used to explore the therapeutic potential of JNK inhibitors for the treatment of cancer, inflammatory diseases, and neurodegenerative disorders. |
| Enzyme Assay |
Radioactive FlashPlates are used as the assay platform for Ser/Thr-kinase assays. 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.
The in vitro kinase assay for JNK Inhibitor VIII involves measuring its ability to inhibit the phosphorylation activity of JNK1, JNK2, or JNK3. The enzyme is incubated with a peptide substrate (e.g., ATF2 or c-Jun) and ATP in the presence of varying concentrations of the compound. The amount of phosphorylated substrate is measured using a luminescent or fluorescent detection system, and the IC50 or Ki is calculated from the dose-response curve. |
| Cell Assay |
HepG2 human hepatoma cells (ATCC) are grown in low glucose MEM with 1×NEAA, 1×sodium pyruvate, and 10% FBS as dietary supplements. Cells are seeded at 5×104 cells/well in 500 μL of complete media on 24-well collagen-coated plates for P-c-Jun assays, and the plates are incubated overnight. The final inhibitor concentrations are provided by adding 5 μL directly to the media on the cells after serial compound dilutions in DMSO at 100×. Cells are stimulated for 30 minutes with TNFR or vehicle control after 1 hour, harvested in 70 μL 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 then frozen at -80 degrees Celsius for use in the P-c-Jun assay.
In vitro cell culture studies for JNK Inhibitor VIII utilize HepG2 cells or other cancer cell lines. Cells are treated with the compound, and the phosphorylation of c-Jun is measured by Western blotting to confirm target inhibition. Cell viability is assessed using MTT assays. Apoptosis is detected by flow cytometry using Annexin V/PI staining. |
| Animal Protocol |
Sprague-Dawley rat
5 mg/kg IV, Oral gavage In vivo animal experiments for JNK Inhibitor VIII are not extensively documented. However, its effects on tumor growth could be studied in xenograft models. Its anti-inflammatory effects could be studied in models of acute inflammation. Its neuroprotective effects could be studied in models of neurodegeneration. Its effects on PTEN null mouse embryonic fibroblast growth could be studied in vivo. |
| ADME/Pharmacokinetics |
JNK Inhibitor VIII has a molecular formula of C22H21N5O and a molecular weight of 371.43 g/mol. It is a solid compound that is soluble in DMSO. It is typically stored as a powder at -20°C for long-term stability. Its stability is maintained under recommended storage conditions. It is a cell-permeable compound.
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| Toxicity/Toxicokinetics |
Toxicological data for JNK Inhibitor VIII are limited, as it is a research compound. It is not intended for human use. Comprehensive toxicity studies have not been reported. Standard safety precautions for handling chemical reagents should be followed. Its potent JNK inhibition suggests it could have significant biological effects.
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| References | |
| Additional Infomation |
JNK Inhibitor VIII is a research compound with no clinical approval. It is a valuable tool for studying JNK signaling pathways and the role of JNK in apoptosis, inflammation, and cancer. It is used in drug discovery programs to explore the therapeutic potential of JNK inhibitors for the treatment of cancer, inflammatory diseases, and neurodegenerative disorders.
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| Molecular Formula |
C₁₈H₂₀N₄O₄
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|---|---|
| Molecular Weight |
356.38
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| Exact Mass |
356.148
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| Elemental Analysis |
C, 60.66; H, 5.66; N, 15.72; O, 17.96
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| CAS # |
894804-07-0
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| Related CAS # |
894804-07-0
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| PubChem CID |
11624601
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
658.6±55.0 °C at 760 mmHg
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| Flash Point |
352.1±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.599
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| LogP |
4.86
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
26
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| Complexity |
509
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N#CC1C(N)=CC(NC(CC2C(OC)=CC=C(OC)C=2)=O)=NC=1OCC
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| InChi Key |
KQMPRSZTUSSXND-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N4O4/c1-4-26-18-13(10-19)14(20)9-16(22-18)21-17(23)8-11-7-12(24-2)5-6-15(11)25-3/h5-7,9H,4,8H2,1-3H3,(H3,20,21,22,23)
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| Chemical Name |
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamide
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| Synonyms |
TCS-JNK-6o; TCS-JNK 6o; TCS JNK-6o; JNK Inhibitor VIII; c-Jun N-terminal Kinase Inhibitor VIII
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 71~250 mg/mL (199.2~701.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8060 mL | 14.0300 mL | 28.0599 mL | |
| 5 mM | 0.5612 mL | 2.8060 mL | 5.6120 mL | |
| 10 mM | 0.2806 mL | 1.4030 mL | 2.8060 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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