| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CYP1A2 1.7 μM (IC50) CYP1A2 2.6 μM (Ki)
Lysine-specific demethylase 1 (LSD1); also inhibits CYP1A2 (non-competitive). |
|---|---|
| ln Vitro |
4,5-Dimethoxycanthin-6-one, with an IC50 value of 1.7μM and a Ki value of 2.6 μM, is a strong and uncompetitive inhibitor of CYP1A2-mediated phenacetin O-deethylation[2].
As an LSD1 inhibitor, it inhibits the proliferation of glioblastoma U251 and T98G cells and induces apoptosis and pyroptosis. It is a potent and uncompetitive inhibitor of CYP1A2-mediated phenacetin O-deethylation (IC50: 1.7 microM, Ki: 2.6 microM). It also shows antibacterial activity against Staphylococcus aureus and cytotoxicity against U937 and HepG2 cancer cell lines. |
| Enzyme Assay |
The LSD1 enzyme inhibition assay measures the demethylation of a biotinylated histone H3 peptide substrate. The compound and enzyme are incubated, followed by addition of the peptide substrate. After reaction, the demethylated product is detected by fluorescence or ELISA using a specific antibody. The assay includes controls for NADH consumption and reaction is stopped by adding acid.
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| Cell Assay |
U251 and T98G human glioblastoma cells are seeded in 96-well plates and treated with compound for 48-72 hours. Cell viability is assessed by MTT or CCK-8 assays. Apoptosis is evaluated by Annexin V-FITC/PI double staining using flow cytometry. Pyroptosis is assessed by measuring LDH release, caspase-1 activation, and morphological changes (cell swelling/membrane rupture).
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| Animal Protocol |
In vivo activity is studied using mouse xenograft models. Immunocompromised mice (e.g., BALB/c nude) are subcutaneously implanted with U251 glioblastoma cells. When tumors reach a specific volume, the compound is administered intraperitoneally or orally at multiple dose levels daily for 2-3 weeks. Tumor volume and body weight are monitored. TUNEL and Ki-67 staining are performed on harvested tumors.
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| ADME/Pharmacokinetics |
Detailed PK data are not publicly available. As a small molecule alkaloid, its absorption, distribution, metabolism, and excretion properties require further characterization. Its bioavailability and plasma half-life would need to be determined in standard rodent PK studies.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are available. As a natural product-derived LSD1 inhibitor, standard toxicity screening in vitro (cytotoxicity panels) and in vivo (rodent acute toxicity) would be necessary for preclinical development. This compound is for research use only.
|
| References | |
| Additional Infomation |
Methylnicarone is a type of β-carboline compound. It has been reported that 4,5-dimethoxycansin-6-one exists in Annona squamosa, Tongkat Ali, and Sophora flavescens, and relevant data are available.
This compound is a research chemical, not an approved drug. It represents a novel class of LSD1 inhibitors with potential for treating glioblastoma. It has dual activities as both an LSD1 inhibitor and a CYP1A2 inhibitor, which could lead to drug-drug interactions in combination therapies. The compound exhibits multiple mechanisms of action including LSD1 inhibition, CYP1A2 inhibition, antibacterial activity, and cancer cell cytotoxicity. |
| Molecular Formula |
C16H12N2O3
|
|---|---|
| Molecular Weight |
280.28
|
| Exact Mass |
280.084
|
| CAS # |
18110-87-7
|
| PubChem CID |
638215
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
455.1±45.0 °C at 760 mmHg
|
| Melting Point |
145-146 °C
|
| Flash Point |
229.0±28.7 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.688
|
| LogP |
2.16
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
21
|
| Complexity |
490
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=C(C(=O)N2C3=CC=CC=C3C4=C2C1=NC=C4)OC
|
| InChi Key |
ATONBUGCNDSBBC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H12N2O3/c1-20-14-12-13-10(7-8-17-12)9-5-3-4-6-11(9)18(13)16(19)15(14)21-2/h3-8H,1-2H3
|
| Chemical Name |
3,4-dimethoxy-1,6-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-3,5(16),6,8,10,12,14-heptaen-2-one
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 10 mg/mL (35.68 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (3.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (3.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5679 mL | 17.8393 mL | 35.6786 mL | |
| 5 mM | 0.7136 mL | 3.5679 mL | 7.1357 mL | |
| 10 mM | 0.3568 mL | 1.7839 mL | 3.5679 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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