| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
(-)-Cephaeline dihydrochloride targets CYP2D6, a cytochrome P450 enzyme involved in the metabolism of many drugs and xenobiotics. CYP2D6 reveals the highest metabolic activity for the generation of 9-O-demethylemetine, and also shows significant metabolic activity for the generation of cephaeline. The compound's anticancer activity in prostate cancer cells suggests additional cellular targets.
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| ln Vitro |
The enzyme CYP2D6 exhibited the highest metabolic activity towards 9-O-demethyl-Emetine. It also demonstrated a noteworthy metabolic activity towards Cephaeline. Cephaeline has an IC50 above 1000, 121, and 1000 μM for CYP2C9, CYP2D6, and CYP3A4, respectively. To find cephaeline's inhibitory constant (Ki) on CYP2D6 and CYP3A4 activities, more tests were carried out. Dixon plots at various Cephaeline concentrations were graphically analyzed for each of the two CYP enzyme assays, with Ki values of 54 and 355 μM for CYP2D6 and CYP3A4, respectively. 1].
In vitro, (-)-Cephaeline dihydrochloride is a selective CYP2D6 inhibitor with an IC50 of 121 microM. CYP2D6 shows the highest metabolic activity for the generation of 9-O-demethylemetine, whereas this enzyme also shows significant metabolic activity for the generation of cephaeline. The compound has been shown to have anticancer activity in prostate cancer cells. |
| ln Vivo |
In vivo activity of (-)-Cephaeline dihydrochloride is inferred from its mechanism as a CYP2D6 inhibitor and its anticancer activity in prostate cancer cells. As a CYP2D6 inhibitor, the compound may affect the metabolism of drugs that are substrates of this enzyme. Its anticancer activity suggests potential therapeutic applications, though detailed in vivo data are limited. The compound is a natural product and is available for research purposes.
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| Enzyme Assay |
The in vitro enzyme assay for (-)-Cephaeline dihydrochloride involves measuring CYP2D6 inhibition. Human liver microsomes or recombinant CYP2D6 are incubated with varying concentrations of (-)-Cephaeline (typically 0.1-1000 uM) and a CYP2D6-specific substrate such as dextromethorphan or bufuralol in assay buffer containing NADPH at 37degC for 10-30 minutes. The reaction is stopped by the addition of acetonitrile or other suitable solvent. Metabolite formation (dextrorphan or 1'-hydroxybufuralol) is measured by LC-MS/MS or HPLC with fluorescence detection. The IC50 is determined by fitting inhibition data to a dose-response curve.
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| Cell Assay |
In vitro cellular assays for (-)-Cephaeline dihydrochloride are conducted using prostate cancer cell lines to assess its anticancer activity. Cells are seeded in 96-well plates and treated with varying concentrations of (-)-Cephaeline (typically 0.1-100 uM) for 24-72 hours. Cell viability is assessed using MTT, CellTiter-Glo, or crystal violet staining assays. Apoptosis is evaluated using Annexin V-FITC/PI double staining or by measuring caspase-3/7 activity. CYP2D6 activity in cell lysates can be measured using fluorogenic substrates. Gene expression changes are analyzed by qPCR.
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| Animal Protocol |
In vivo animal studies for (-)-Cephaeline dihydrochloride are not extensively documented. As a research compound with anticancer activity in prostate cancer cells, typical studies would involve xenograft models in immunodeficient mice bearing prostate cancer cell lines. The compound would be administered by intraperitoneal injection at doses determined from preliminary pharmacokinetic and tolerability studies. Tumor growth inhibition would be assessed, and standard toxicology parameters including body weight and clinical observations would be monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (-)-Cephaeline dihydrochloride are not extensively documented. The compound has a molecular weight of 539.53 and a molecular formula of C28H40Cl2N2O4. It is soluble in DMSO at 150 mg/mL. As a natural alkaloid, it is expected to have good oral bioavailability and the ability to cross biological membranes. The compound should be stored at 2-8degC. Detailed ADME parameters are not available in the published literature.
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| Toxicity/Toxicokinetics |
The toxicological profile of (-)-Cephaeline dihydrochloride has not been extensively characterized. As a natural alkaloid and CYP2D6 inhibitor, the compound may have effects on drug metabolism and potential toxicity at high doses. The compound is for research use only and is not intended for human therapeutic use. Standard safety precautions should be followed when handling the compound in a laboratory setting. No specific LD50 values have been reported.
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| References | |
| Additional Infomation |
(-)-Cephaeline dihydrochloride (CAS 5853-29-2) is a selective CYP2D6 inhibitor with an IC50 of 121 microM. It is also known as NSC 32944. The compound is a natural product that has been shown to have anticancer activity in prostate cancer cells. CYP2D6 shows the highest metabolic activity for the generation of 9-O-demethylemetine, whereas this enzyme also shows significant metabolic activity for the generation of cephaeline. It is available for research purposes only.
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| Molecular Formula |
C28H39CLN2O4
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|---|---|
| Molecular Weight |
503.0733
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| Exact Mass |
538.236
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| CAS # |
5853-29-2
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| PubChem CID |
23615629
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| Appearance |
White to off-white solid powder
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| LogP |
5.709
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
664
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC[C@H]1CN2CCC3=CC(=C(C=C3[C@@H]2C[C@@H]1C[C@@H]4C5=CC(=C(C=C5CCN4)O)OC)OC)OC.Cl.Cl
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| InChi Key |
YAOHSWWVTZSRQM-JBKGYMEJSA-N
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| InChi Code |
InChI=1S/C28H38N2O4.2ClH/c1-5-17-16-30-9-7-19-13-27(33-3)28(34-4)15-22(19)24(30)11-20(17)10-23-21-14-26(32-2)25(31)12-18(21)6-8-29-23;;/h12-15,17,20,23-24,29,31H,5-11,16H2,1-4H3;2*1H/t17-,20-,23+,24-;;/m0../s1
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| Chemical Name |
(1R)-1-[[(2S,3R,11bS)-3-ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]methyl]-7-methoxy-1,2,3,4-tetrahydroisoquinolin-6-ol;dihydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~463.37 mM)
H2O : ~125 mg/mL (~231.68 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.86 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.86 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. View More
Solubility in Formulation 3: 50 mg/mL (92.67 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9878 mL | 9.9390 mL | 19.8779 mL | |
| 5 mM | 0.3976 mL | 1.9878 mL | 3.9756 mL | |
| 10 mM | 0.1988 mL | 0.9939 mL | 1.9878 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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