| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Bazedoxifene N-Oxide shares the core benzothiophene structure of bazedoxifene and is expected to interact with estrogen receptors (ERalpha and ERbeta). Bazedoxifene functions as a SERM, acting as an estrogen antagonist in breast and uterine tissues but as an agonist on bone, lipid metabolism, and the urogenital tract. The N-oxide metabolite is predicted to have reduced activity at the estrogen receptor compared to the parent drug due to the addition of a polar, charged oxygen atom on the amine, which may impair receptor binding affinity and cellular penetration.
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| ln Vitro |
While the parent drug bazedoxifene exhibits potent binding to estrogen receptors (IC₅0 values around 2-10 nM for displacement of estradiol), specific in vitro activity data for Bazedoxifene N-Oxide is not publicly available. As an N-oxide metabolite, it is expected to be less active than bazedoxifene in estrogen response element (ERE)-luciferase reporter assays. In such assays, bazedoxifene typically shows partial agonist activity in bone cells (e.g., SaOS-2) and antagonist activity in breast cells (e.g., MCF-7). The N-oxide likely has reduced potency in both contexts.
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| ln Vivo |
No specific in vivo activity data for Bazedoxifene N-Oxide is available. The parent drug bazedoxifene is administered orally and is primarily metabolized by glucuronidation, with N-oxide formation being a minor oxidative pathway. The N-oxide metabolite is not believed to contribute significantly to the therapeutic efficacy of bazedoxifene in vivo, as its concentration in plasma is likely low and its receptor binding affinity is reduced compared to the parent drug. Animal studies focus on bazedoxifene, not its N-oxide degradant.
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| Enzyme Assay |
Non-cellular binding assays for Bazedoxifene N-Oxide would follow established protocols for SERM screening. A standard ERalpha binding assay uses the LanthaScreen TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) method. The test compound (Bazedoxifene N-Oxide) is serially diluted in assay buffer (50 mM Tris-HCl pH 7.5, 100 mM KCl, 1 mM DTT, 0.1% BSA) and mixed with purified human ERalpha-LBD (ligand-binding domain), terbium-labeled anti-GST antibody, and a fluorescein-labeled estrogen ligand. After incubation for 2 hours at room temperature, TR-FRET ratios (520 nm/495 nm) are measured. The IC₅0 is calculated as the concentration required to displace 50% of the labeled estrogen.
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| Cell Assay |
Cellular assays to evaluate estrogen receptor activity typically use reporter cell lines. A standard protocol uses MCF-7 cells stably transfected with an ERE-luciferase reporter (ERE-Luc). Cells are seeded in 96-well plates at 20,000 cells/well in phenol red-free DMEM with charcoal-stripped FBS for 24 hours. Cells are treated with Bazedoxifene N-Oxide (0.01 nM to 10 microM) for 24 hours. Luciferase activity is measured using a luminometer after addition of luciferin substrate. Parallel wells are treated with 0.1 nM estradiol as a positive control to determine antagonist activity. Results are expressed as percent of estradiol-induced luciferase activity.
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| Animal Protocol |
In vivo experiments for bazedoxifene utilize the ovariectomized (OVX) rat model of estrogen deficiency. Female Sprague-Dawley rats undergo bilateral ovariectomy at 12 weeks of age. After a 14-day recovery, rats are administered bazedoxifene (0.1-10 mg/kg/day) or vehicle (control) by oral gavage for 4 weeks. Primary endpoints include uterine weight (to measure estrogen agonism/antagonism), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), and serum cholesterol levels. Since Bazedoxifene N-Oxide is not the active drug, it would not be tested in such models.
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| ADME/Pharmacokinetics |
Bazedoxifene N-Oxide has a molecular formula of C30H34N2O4 and a molecular weight of 486.60 g/mol, compared to bazedoxifene (C30H34N2O3, 470.60 g/mol). The addition of the oxygen atom increases the polarity of the molecule, likely reducing its logP value and increasing aqueous solubility. The N-oxide is generally more hydrophilic than the parent tertiary amine. It can be analyzed by reverse-phase HPLC with UV detection at 220 nm or by LC-MS/MS in positive ion mode using electrospray ionization, monitoring the transition m/z 487 → 470 (loss of oxygen).
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| Toxicity/Toxicokinetics |
As a pharmaceutical impurity and metabolite, Bazedoxifene N-Oxide is present at low levels in bazedoxifene drug products. Regulatory guidelines (ICH Q3A/Q3B) set qualification thresholds for impurities. The toxicological profile of the N-oxide is expected to be similar to, but less potent than, bazedoxifene. However, no specific toxicity studies are available. In general, N-oxide metabolites of tertiary amines can be reduced back to the parent amine by gut microflora or liver enzymes, potentially contributing to parent drug activity. Standard safety precautions for handling pharmaceutical reference standards apply.
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| References | |
| Additional Infomation |
Bazedoxifene N-Oxide is not a drug and has no therapeutic use. It is an impurity reference standard used exclusively for pharmaceutical quality control. The compound is employed to develop and validate HPLC and LC-MS/MS methods for monitoring degradation products in bazedoxifene formulations. Bazedoxifene itself (marketed under the trade name Duavee in combination with conjugated estrogens) is an FDA-approved SERM for treating osteoporosis and vasomotor symptoms in postmenopausal women. The N-oxide impurity is required to be controlled to ≤0.1% in the drug substance per ICH guidelines.
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| Molecular Formula |
C30H34N2O4
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|---|---|
| Molecular Weight |
486.60
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| Exact Mass |
486.252
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| CAS # |
1174289-22-5
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| PubChem CID |
59499290
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| Appearance |
Typically exists as solids at room temperature
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| LogP |
6.302
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
668
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1C=CC(C2=C(C)C3C=C(C=CC=3N2CC2C=CC(OCC[N+]3(CCCCCC3)[O-])=CC=2)O)=CC=1
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| InChi Key |
CFBANWAZVCOMGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H34N2O4/c1-22-28-20-26(34)12-15-29(28)31(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)36-19-18-32(35)16-4-2-3-5-17-32/h6-15,20,33-34H,2-5,16-19,21H2,1H3
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| Chemical Name |
2-(4-hydroxyphenyl)-3-methyl-1-[[4-[2-(1-oxidoazepan-1-ium-1-yl)ethoxy]phenyl]methyl]indol-5-ol
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| Synonyms |
Bazedoxifene N-oxide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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 | 2.0551 mL | 10.2754 mL | 20.5508 mL | |
| 5 mM | 0.4110 mL | 2.0551 mL | 4.1102 mL | |
| 10 mM | 0.2055 mL | 1.0275 mL | 2.0551 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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