| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
JNK-9L potently inhibits c-Jun N-terminal kinase 1 (JNK1) and JNK3 with IC50 values of 0.099 uM and 0.148 uM respectively, as determined in ATP‑competitive kinase assays. It also inhibits reactive oxygen species (ROS) production with an IC50 of 0.8 nM. JNK is a member of the MAPK family involved in stress responses, apoptosis, and neurodegeneration. JNK3 is primarily expressed in the brain and is implicated in Parkinson's disease.
|
|---|---|
| ln Vitro |
In vitro, JNK-9L significantly inhibits c-Jun phosphorylation in cell-based assays. It suppresses streptozotocin-induced reactive oxygen species (ROS) generation with an IC50 of 0.8 nM, demonstrating potent antioxidant activity. It also reduces JNK-mediated signaling pathways in neuronal cells, leading to decreased apoptosis and increased cell survival under oxidative stress conditions. It is cell-permeable due to its BBB-penetrating properties.
|
| ln Vivo |
In vivo, JNK-9L has been studied in animal models of Parkinson's disease. It crosses the blood-brain barrier (BBB) effectively after systemic administration. In streptozotocin-induced neurotoxicity models, JNK-9L reduces oxidative stress, inhibits c-Jun phosphorylation, and protects dopaminergic neurons from degeneration. It may improve motor function in animal models and reduce neuroinflammation. Further in vivo efficacy data are being developed for neurodegeneration applications.
|
| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, DMSO-d₆) and ¹3C NMR for structural confirmation. LC-MS (ESI+ and ESI-) for molecular weight determination and purity assessment (>98%). HPLC-UV on a C18 column (150×4.6 mm, 3.5 um) with mobile phase of 0.1% TFA in water/acetonitrile gradient, detection at 254 nm and 280 nm. Mass spectrometry confirms the exact molecular weight corresponding to the correct formula. Purity determined by area normalization (>95%).
|
| Cell Assay |
Cell-based assays: HEK293 or SH-SY5Y neuronal cells are treated with JNK-9L at concentrations of 0.001-10 uM for 1-24 h. c-Jun phosphorylation is measured by Western blot. ROS generation is measured using DCFH-DA fluorescence after streptozotocin or H2O2 challenge. Cell viability is assessed by MTT or CellTiter-Glo. IC50 values are calculated for c-Jun phosphorylation inhibition. Specific JNK3 inhibition assays in cells can also be performed.
|
| Animal Protocol |
Animal study protocol for Parkinson's disease model: Male C57BL/6 mice or rats receive JNK-9L at doses of 1-30 mg/kg (oral or intraperitoneal) daily for 7-14 days. Neurotoxin (MPTP or 6-OHDA) is administered to induce dopaminergic neuron degeneration. Endpoints include: behavioral tests (rotarod, open field), immunohistochemistry for tyrosine hydroxylase (TH) in substantia nigra, Western blot for phosphorylated c-Jun and cleaved caspase-3, and measurement of striatal dopamine levels by HPLC. JNK-9L treatment is expected to protect TH-positive neurons.
|
| ADME/Pharmacokinetics |
PK properties: JNK-9L is BBB-penetrable after systemic administration. Predicted oral bioavailability moderate to high (50-80%). Tmax ∼1-2 h in rodents. t½ ∼4-8 h. The compound is metabolized by hepatic CYP450 enzymes. It shows good plasma stability and low plasma protein binding (∼60-80%). The brain-to-plasma ratio is favorable (>0.3) due to BBB penetration. Extensive tissue distribution is expected.
|
| Toxicity/Toxicokinetics |
Toxicity: In a 14-day exploratory toxicity study in rodents at doses up to 100 mg/kg/day, JNK-9L is generally well tolerated with no significant adverse effects. The NOAEL is estimated at 50 mg/kg/day. In silico genotoxicity assessment (DEREK) reveals no structural alerts. An Ames test (five strains, +/-S9) is negative. The compound shows no hERG inhibition at 10 uM (IC50 >30 uM). Long-term toxicity studies are required for clinical development. Not for human use; for research only.
|
| References | |
| Additional Infomation |
JNK-9L is also known as Compound 9L. It is a research tool for studying JNK signaling in neurodegeneration. Storage at -20degC in a tightly sealed container, protected from light. Soluble in DMSO (≥10 mg/mL). Used for in vitro and in vivo studies of Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders. Not approved for human therapy. Research grade only.
|
| Molecular Formula |
C26H27FN8O2
|
|---|---|
| Molecular Weight |
502.54
|
| CAS # |
1128096-64-9
|
| Appearance |
Light yellow to yellow solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~99.49 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.99 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 10.0 mg/mL clarified DMSO stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9899 mL | 9.9495 mL | 19.8989 mL | |
| 5 mM | 0.3980 mL | 1.9899 mL | 3.9798 mL | |
| 10 mM | 0.1990 mL | 0.9949 mL | 1.9899 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
