| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
2.49 nM (EGFR), 3.95 nM (p-wtEGFR), 4.48 nM (pEGFRvⅢ)[1].
JCN037 targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It is a non-covalent inhibitor that is effective against various EGFR forms, including wild-type EGFR and the mutant EGFRvIII. Its ability to penetrate the blood-brain barrier extends its potential in neuro-oncological research, particularly for brain tumors. |
|---|---|
| ln Vitro |
In HK301 cells and GBM39 cells, JCN037 displays GI50 values of 329 nM and 1116 nM, respectively[1].
In vitro, JCN037 demonstrates potent inhibitory activity against EGFR with IC50 values of 2.49 nM for EGFR, 3.95 nM for p-wtEGFR, and 4.48 nM for pEGFRvIII. Its activity is assessed using biochemical kinase assays and cell-based assays in cancer cell lines. These studies confirm its effectiveness in inhibiting various EGFR forms. |
| ln Vivo |
Due to a fast hydroxylation of the fused 1,4-dioxane ring, compound 5, JCN037, shows limited oral bioavailability, indicating first pass metabolism[1]. Treatment with JCN037 (compound 5, 300 mg/kg, BID) significantly improves survival; median survival improved from 37.5 days to 55 days with 5 treatment, a 47% increase[1].
In vivo, JCN037 has been studied in animal models of cancer, particularly those involving brain tumors due to its BBB permeability. Its ability to penetrate the blood-brain barrier makes it a valuable tool for studying EGFR-driven malignancies in the central nervous system. |
| Enzyme Assay |
Cell-free assays for JCN037 typically involve measuring its inhibitory activity against wild-type and mutant EGFR kinases using biochemical kinase assays. The IC50 values of 2.49 nM, 3.95 nM, and 4.48 nM for EGFR, p-wtEGFR, and pEGFRvIII, respectively, are determined by measuring the phosphorylation of a substrate in the presence of varying concentrations of the inhibitor.
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| Cell Assay |
Western Blot Analysis[1].
Cell Types: GBM39 and GS025 cells. Tested Concentrations: 0-3333 nM Incubation Duration: Experimental Results: Downregulated pEGFRvⅢ , p Akt, p-ERK, and p-S6 protein levels, dramatically. In vitro cellular assays are conducted to evaluate the functional activity of JCN037. Cancer cell lines expressing various EGFR forms are treated with the compound. Cell viability and proliferation are measured to assess the compound's anti-proliferative effects. EGFR phosphorylation is also measured to confirm inhibition of the target kinase. |
| Animal Protocol |
In vivo animal experiments typically involve xenograft models of brain tumors or other EGFR-driven cancers. Mice bearing these tumors are administered JCN037. Tumor growth is monitored over time to assess the compound's efficacy. These studies are essential for demonstrating the in vivo antitumor activity of the compound.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of JCN037 are characterized by its ability to penetrate the blood-brain barrier. Its molecular weight is 376.18. The compound is designed to have favorable drug-like properties to support efficacy in the central nervous system.
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| Toxicity/Toxicokinetics |
The toxicity profile of JCN037 is not extensively documented but is likely to be similar to other EGFR inhibitors. Common adverse effects may include skin rash and diarrhea. Its BBB permeability may also lead to central nervous system-related side effects. Preclinical studies would typically involve acute and chronic dosing in animal models to assess safety margins.
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| References | |
| Additional Infomation |
JCN037 is a research compound that targets EGFR with potent activity and blood-brain barrier permeability. It is a valuable tool for studying EGFR-driven malignancies, particularly in the central nervous system. The compound is not approved for therapeutic use and is intended for research purposes only.
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| Molecular Formula |
C16H11BRFN3O2
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|---|---|
| Molecular Weight |
376.179846048355
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| Exact Mass |
375.001
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| CAS # |
2305154-31-6
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| PubChem CID |
138513760
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
BrC1=CC=CC(=C1F)NC1C2=CC3=C(C=C2N=CN=1)OCCO3
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| InChi Key |
MTLUFWWVOINWEL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11BrFN3O2/c17-10-2-1-3-11(15(10)18)21-16-9-6-13-14(23-5-4-22-13)7-12(9)19-8-20-16/h1-3,6-8H,4-5H2,(H,19,20,21)
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| Chemical Name |
N-(3-bromo-2-fluorophenyl)-7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-4-amine
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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: 250 mg/mL (664.58 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (16.61 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 2.6583 mL | 13.2915 mL | 26.5830 mL | |
| 5 mM | 0.5317 mL | 2.6583 mL | 5.3166 mL | |
| 10 mM | 0.2658 mL | 1.3292 mL | 2.6583 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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