| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
CYP2C19
|
|---|---|
| ln Vitro |
The enantiomers exhibit potent and selective inhibition of CYP2C19: (+)-N-3-Benzylnirvanol has a Ki of 0.25 uM (0.292 uM), while (-)-N-3-Benzylnirvanol has a Ki of 5.3 uM. Both enantiomers are potent and specific cytochrome P450 inhibitors with Kis of 0.25 and 5.3 uM for CYP2C19, respectively. The racemate is used in pharmacological research to study the effects of CYP2C19 inhibition on drug metabolism and cholesterol homeostasis.
|
| ln Vivo |
(+/-)-N-3-Benzylnirvanol (20 mg/kg, i.p.) lowers plasma levels of cholesterol in mice. This demonstrates that the racemate has hypocholesterolemic effects in vivo. The enantiomers selectively inhibit CYP2C19 in vitro, while the racemate has demonstrated cholesterol-lowering effects in murine in vivo studies. The exact mechanism linking CYP2C19 inhibition to cholesterol lowering is not fully understood but is an area of active research.
|
| Enzyme Assay |
Recombinant human CYP2C19 is expressed in insect cells or E. coli and reconstituted with NADPH-cytochrome P450 reductase and cytochrome b5. The enzyme activity assay uses a fluorogenic or luminogenic substrate (e.g., 3-cyano-7-ethoxycoumarin (CEC) or Luciferin-H) or a specific CYP2C19 substrate such as (S)-mephenytoin. The reaction is incubated at 37degC for 10-30 minutes in a buffer containing potassium phosphate (pH 7.4), MgCl2, and an NADPH-regenerating system. Product formation is measured by fluorescence, luminescence, or LC-MS. Inhibition constants (Ki values) are determined by measuring enzyme activity at varying inhibitor concentrations and substrate concentrations. Ki values are calculated using Dixon plots or non-linear regression analysis.
|
| Cell Assay |
Primary human hepatocytes or CYP2C19-overexpressing cell lines (e.g., HEK293-CYP2C19) are cultured in appropriate media. Cells are treated with (+/-)-N-3-Benzylnirvanol (0.1-100 uM) for 1-24 hours in the presence of a CYP2C19 probe substrate (e.g., (S)-mephenytoin or omeprazole). The metabolite (e.g., 4'-hydroxymephenytoin or 5-hydroxyomeprazole) is quantified in the culture medium by LC-MS/MS. CYP2C19 enzyme activity is expressed as the metabolite formation rate relative to controls. Cell viability is assessed by MTT or LDH assays. The effect of CYP2C19 inhibition on drug-drug interactions can be studied by co-incubating with drugs metabolized by CYP2C19.
|
| Animal Protocol |
Male mice (typically C57BL/6 or other strains) are used for in vivo efficacy studies. (+/-)-N-3-Benzylnirvanol is formulated in a suitable vehicle (e.g., 10% DMSO in PBS, or 0.5% methylcellulose) and administered intraperitoneally (i.p.) at a dose of 20 mg/kg. The dosing regimen may be single dose or repeated doses (e.g., daily for 7-14 days). Blood samples are collected at various time points (0-48 hours) from the tail vein or by cardiac puncture. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides are measured by enzymatic colorimetric assays. CYP2C19 activity in liver microsomes can be assessed ex vivo by incubating with probe substrates and measuring metabolite formation by LC-MS/MS. Liver histology is also evaluated for signs of toxicity.
|
| ADME/Pharmacokinetics |
No specific pharmacokinetic data for (+/-)-N-3-Benzylnirvanol. Based on the compound's properties (molecular weight ~306, logP estimation), it is likely to have moderate oral bioavailability and distribution. For in vivo studies, it is typically administered intraperitoneally (i.p.) at 20 mg/kg. Specific PK parameters (half-life, Cmax, AUC, clearance, volume of distribution) are not publicly available but can be determined experimentally. Metabolism is likely mediated by CYP enzymes, and drug-drug interaction potential exists.
|
| Toxicity/Toxicokinetics |
No specific toxicity data for (+/-)-N-3-Benzylnirvanol. In mice, at the tested dose of 20 mg/kg i.p., the compound does not cause overt signs of acute toxicity (e.g., seizures, respiratory distress, death). No significant effects on body weight or general health are reported in the available literature. Long-term safety and chronic toxicity studies have not been published. As a CYP2C19 inhibitor, the primary expected on-target effect is altered metabolism of CYP2C19 substrate drugs, potentially leading to drug-drug interactions.
|
| References | |
| Additional Infomation |
(+/-)-N-3-Benzylnirvanol (CAS: 93879-40-4) is a research tool for studying cytochrome P450 enzyme inhibition, particularly CYP2C19. The enantiomers (+)-N-3-Benzylnirvanol (Ki = 0.25 uM) and (-)-N-3-Benzylnirvanol (Ki = 5.3 uM) have distinct inhibitory potencies. The racemate has demonstrated cholesterol-lowering effects in mice at 20 mg/kg i.p. The compound is not approved for clinical use. Molecular formula: C18H18N2O2. Synonyms: (+/-)N3Benzylnirvanol, (+/-) N 3 Benzylnirvanol, (+/-)-N-3-苄基神经醇, N-3-Benzylnirvanol. It is supplied as a powder with purity >97%. References include the use of this compound in pharmacological research.
|
| Molecular Formula |
C18H18N2O2
|
|---|---|
| Molecular Weight |
294.35
|
| Exact Mass |
294.137
|
| CAS # |
93879-40-4
|
| PubChem CID |
4804492
|
| Appearance |
White to off-white solid powder
|
| Density |
1.19g/cm3
|
| Melting Point |
134-136ºC
|
| Index of Refraction |
1.593
|
| LogP |
3.31
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
22
|
| Complexity |
425
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCC1(C(=O)N(C(=O)N1)CC2=CC=CC=C2)C3=CC=CC=C3
|
| InChi Key |
ZMZDHUHMXXALFX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H18N2O2/c1-2-18(15-11-7-4-8-12-15)16(21)20(17(22)19-18)13-14-9-5-3-6-10-14/h3-12H,2,13H2,1H3,(H,19,22)
|
| Chemical Name |
3-benzyl-5-ethyl-5-phenylimidazolidine-2,4-dione
|
| 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: 250 mg/mL (849.33 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3973 mL | 16.9866 mL | 33.9732 mL | |
| 5 mM | 0.6795 mL | 3.3973 mL | 6.7946 mL | |
| 10 mM | 0.3397 mL | 1.6987 mL | 3.3973 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
