| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The primary target of N-Nornuciferine is cytochrome P450 2D6 (CYP2D6), a key enzyme involved in the metabolism of many drugs. The compound competitively inhibits CYP2D6-catalyzed dextromethorphan O-demethylation with a Ki of 2.34 μM. It shows weak or no inhibition of other CYP450 isoenzymes including CYP2C19, CYP3A4, CYP2E1, and CYP2C9. N-Nornuciferine also interacts with dopamine and serotonin receptors, modulating neuronal signaling. The compound is an orally active, blood-brain barrier-permeable CYP2D6 inhibitor.
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| ln Vitro |
Lotus leaf is a widely used traditional Chinese medicine that has a variety of physiological and pharmacological effects, particularly lowering cholesterol and blood triglyceride levels. The four P450 isoenzymes (CYP2C19, CYP3A4, CYP2E1, and CYP2C9) are all weakly or not inhibited by N-nornuciferine, whereas CYP2D6 activity is severely inhibited. With an apparent Ki value of 2.34 μM, n-nitroferine competitively inhibits the ortho-position demethylation of dextromethorphan catalyzed by CYP2D6[1].
In vitro, N-Nornuciferine demonstrates potent inhibition of CYP2D6 enzyme activity with an IC50 of 3.76 μM and a Ki of 2.34 μM. It competitively inhibits CYP2D6-mediated dextromethorphan O-demethylation. The compound shows weak or negligible inhibition toward other major P450 isoenzymes including CYP2C19, CYP3A4, CYP2E1, and CYP2C9. N-Nornuciferine’s selectivity for CYP2D6 makes it a valuable tool for studying CYP2D6-related drug metabolism and herb–drug interactions. The compound also exhibits anti-inflammatory activity. |
| ln Vivo |
In vivo, N-Nornuciferine is orally active and blood-brain barrier-permeable. As a CYP2D6 inhibitor, it has potential effects on the metabolism of co-administered drugs that are CYP2D6 substrates. The compound’s interaction with dopamine and serotonin receptors suggests potential antidepressant and neuroprotective effects in vivo. It has been studied for its lipid-lowering and metabolic regulatory activities. Further in vivo studies are needed to fully characterize its pharmacokinetic and pharmacodynamic properties.
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| Enzyme Assay |
In vitro enzyme assays for N-Nornuciferine involve measuring CYP2D6 activity using specific substrates such as dextromethorphan. The compound’s IC50 of 3.76 μM and Ki of 2.34 μM are determined through enzyme kinetic studies. CYP2D6-mediated O-demethylation of dextromethorphan is monitored by HPLC or LC-MS/MS. Inhibition of other CYP450 isoenzymes (CYP2C19, CYP3A4, CYP2E1, CYP2C9) is assessed using isoform-specific substrates to confirm selectivity. Assays are performed in human liver microsomes or recombinant CYP450 enzyme systems. Positive controls (e.g., quinidine for CYP2D6) are used for validation.
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| Cell Assay |
In vitro cell-based assays for N-Nornuciferine are conducted in cell lines expressing CYP2D6 or relevant receptor systems. For CYP2D6 inhibition studies, cells are treated with the compound and a CYP2D6 substrate, and metabolite formation is measured. For neurotransmitter receptor studies, cells expressing dopamine or serotonin receptors are used to assess receptor binding and signaling modulation. Cell viability is assessed by standard assays. Anti-inflammatory activity may be evaluated in LPS-stimulated macrophages. Experiments are performed in triplicate with appropriate positive and negative controls. IC50 and Ki values are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies for N-Nornuciferine are conducted in rodent models. For CYP2D6 inhibition studies, rats or mice are administered the compound orally, and the pharmacokinetics of a CYP2D6 probe substrate are assessed. For antidepressant or neuroprotective evaluation, behavioral tests such as forced swim test or tail suspension test may be used. For metabolic studies, animals are treated with N-Nornuciferine and metabolic parameters are monitored. Dosing is typically via oral administration. Blood samples are collected for pharmacokinetic analysis. Studies are conducted in accordance with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
N-Nornuciferine (MW 281.35 g/mol, C18H19NO2) is an orally active, blood-brain barrier-permeable compound with favorable drug-like properties. Its molecular formula is C18H19NO2. The compound shows good oral bioavailability as demonstrated by its activity in preclinical studies. N-Nornuciferine is metabolized by hepatic enzymes, and its inhibition of CYP2D6 suggests potential for drug-drug interactions. The compound is distributed to tissues including brain due to its blood-brain barrier permeability. Pharmacokinetic parameters would be determined in species-specific studies.
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| Toxicity/Toxicokinetics |
N-Nornuciferine is generally well-tolerated in preclinical studies. The compound is a natural alkaloid derived from lotus leaf, a traditional Chinese medicinal herb. Its selective CYP2D6 inhibition profile suggests a favorable safety profile compared to non-selective inhibitors. No significant adverse effects have been reported in the available literature at research-use concentrations. The compound is intended for research use only. Standard safety precautions should be followed when handling. Comprehensive toxicological evaluation would be required for therapeutic development.
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| References | |
| Additional Infomation |
N-nornucleotides have been reported to be found in magnolia (Magnolia officinalis), neotsea konishii, and other organisms with available data.
N-Nornuciferine is an aporphine alkaloid isolated from lotus leaf (Nelumbo nucifera). It acts as a potent and selective inhibitor of CYP2D6 with an IC50 of 3.76 μM and a Ki of 2.34 μM. The compound competitively inhibits CYP2D6-mediated dextromethorphan O-demethylation while showing weak inhibition of other CYP450 isoenzymes. N-Nornuciferine also interacts with dopamine and serotonin receptors, exhibiting potential antidepressant and neuroprotective effects. Its high selectivity makes it a valuable tool for studying CYP2D6-related drug metabolism and herb–drug interactions. All applications are limited to non-human research use. |
| Molecular Formula |
C18H19NO2
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| Molecular Weight |
281.3490
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| Exact Mass |
281.141
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| CAS # |
4846-19-9
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| PubChem CID |
12313579
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
446.4±45.0 °C at 760 mmHg
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| Melting Point |
128-129 ºC
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| Flash Point |
182.8±18.2 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.598
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| LogP |
3.23
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
374
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=C(C2=C3[C@@H](CC4=CC=CC=C42)NCCC3=C1)OC
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| InChi Key |
QQKAHDMMPBQDAC-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C18H19NO2/c1-20-15-10-12-7-8-19-14-9-11-5-3-4-6-13(11)17(16(12)14)18(15)21-2/h3-6,10,14,19H,7-9H2,1-2H3/t14-/m1/s1
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| Chemical Name |
(6aR)-1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
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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 : ~100 mg/mL (~355.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.89 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (8.89 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 25.0 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: ≥ 2.5 mg/mL (8.89 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 | 3.5543 mL | 17.7715 mL | 35.5429 mL | |
| 5 mM | 0.7109 mL | 3.5543 mL | 7.1086 mL | |
| 10 mM | 0.3554 mL | 1.7771 mL | 3.5543 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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