| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Arzoxifene targets the estrogen receptor (ER) as a mixed agonist/antagonist. It binds to estrogen receptors and exhibits tissue-selective effects: antagonistic in breast and uterine tissues and agonistic in bone and the cardiovascular system. The compound's IC50 and target specificity are characteristic of the SERM class.
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| ln Vitro |
Azoxifene blocks the growth of cells just as well as tamoxifen, an anti-estrogen. Northern analysis revealed that the expression of progesterone receptor B mRNA and pS2 was statistically significantly inhibited by arzoxifene. The expression of antitrypsin mRNA was shown to be significantly agonistic. As opposed to tamoxifen and estradiol, azoxifen does not increase the expression of cathepsin D mRNA and protein [1].
In vitro, Arzoxifene inhibits cell growth in breast cancer cell lines such as MCF-7 and MDA-MB-231. Northern blot analysis shows that Arzoxifene significantly inhibits pS2 and progesterone receptor B mRNA expression while exhibiting agonistic effects on anti-trypsin mRNA expression. Unlike estradiol and tamoxifen, Arzoxifene does not induce cathepsin D mRNA and protein expression. |
| ln Vivo |
In rats treated with ovariectomy, azoxifene avoided increases in body weight and blood cholesterol levels and, in a dose-dependent manner, brought them down below sham levels; its maximal efficacy was comparable to that of raloxifene or estrogen. Azoxifene (LY353381.HCl) has an ED50 of roughly 0.01 mg/kg and a maximum efficacy of 0.1–1 mg/kg/day in preventing bone loss caused by ovariectomy. Estrogen-induced increases in uterine weight are countered by arzoxifene (LY353381.HCl), which has an ED50 of 0.03 mg/kg/day and returns the weight to vehicle dose control levels [2].
In vivo, Arzoxifene prevents ovariectomy-induced increases in body weight and serum cholesterol levels in rats, reducing them below sham levels in a dose-dependent manner. It prevents ovariectomy-induced bone loss with an ED50 of approximately 0.01 mg/kg, with maximal efficacy observed at 0.1-1 mg/kg/day. It antagonizes estrogen-induced uterine weight increases with an ED50 of 0.03 mg/kg/day. |
| Enzyme Assay |
For receptor binding assays, Arzoxifene is incubated with estrogen receptors isolated from target tissues or recombinant ER proteins. Competitive binding studies using ³H-estradiol are performed to determine binding affinity and selectivity. The compound's ability to compete with estradiol for ER binding is measured by scintillation counting after separation of bound and free ligand.
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| Cell Assay |
Cellular assays are performed using breast cancer cell lines (MCF-7 and MDA-MB-231). Cells are treated with Arzoxifene HCl at concentrations of 0.1, 1, 10, 100, and 1000 nM. Medium is renewed at days 3 and 5, and cell number is determined by hemocytometer counting at day 6. Gene expression analysis for ER-regulated genes is performed by Northern blot or qPCR.
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| Animal Protocol |
In vivo studies are conducted in ovariectomized or intact female rats. Antiestrogen activity is evaluated in 21-day-old Sprague Dawley rats using 17α-ethynyl estradiol at 0.1 mg/kg/day as the estrogenic stimulus. Endpoints include uterine weight, bone mineral density measured by DEXA, and serum cholesterol levels.
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| ADME/Pharmacokinetics |
Arzoxifene HCl (molecular weight 512.06) is a small-molecule SERM with good oral bioavailability. It is soluble in DMSO (25 mg/mL, 48.82 mM) with warming and sonication. The compound is typically formulated for oral administration in preclinical studies and shows favorable pharmacokinetic properties consistent with other SERMs.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have demonstrated that Arzoxifene is well-tolerated with a safety profile characteristic of SERMs. Unlike estrogens, it does not stimulate uterine proliferation, reducing the risk of endometrial hyperplasia. The compound maintains bone density and lowers cholesterol without the adverse effects associated with unopposed estrogen therapy.
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| References | |
| Additional Infomation |
Azoxifen hydrochloride is the hydrochloride salt of azoxifene, a synthetic aromatic derivative with anti-estrogenic properties. Azoxifen acts as a mixed estrogen agonist/antagonist, binding to estrogen receptors. Compared to other selective estrogen receptor modulators (SERMs), azoxifene exhibits higher bioavailability and stronger anti-estrogenic potency in the breast (higher than raloxifene); however, it has lower estrogenic activity in the uterus compared to tamoxifen or raloxifene. This drug may have benefits for the skeletal and cardiovascular systems.
Arzoxifene HCl (LY353381) is a SERM developed by Eli Lilly as a potential alternative to tamoxifen and raloxifene for breast cancer prevention and osteoporosis. Its tissue-selective mechanism allows beneficial effects on bone and cardiovascular system while antagonizing estrogen in breast and uterine tissues. Despite promising preclinical and clinical data, Arzoxifene did not receive regulatory approval for commercial use. |
| Molecular Formula |
C28H29NO4S.HCL
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|---|---|
| Molecular Weight |
512.0601
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| Exact Mass |
511.158
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| CAS # |
182133-27-3
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| Related CAS # |
Arzoxifene;182133-25-1
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| PubChem CID |
179338
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| Appearance |
Off-white to light yellow solid powder
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| Boiling Point |
656.4ºC at 760mmHg
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| Flash Point |
350.8ºC
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| Vapour Pressure |
7.85E-18mmHg at 25°C
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| LogP |
7.679
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
601
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NHSNLUIMAQQXGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H29NO4S.ClH/c1-31-22-8-5-20(6-9-22)28-27(25-14-7-21(30)19-26(25)34-28)33-24-12-10-23(11-13-24)32-18-17-29-15-3-2-4-16-29;/h5-14,19,30H,2-4,15-18H2,1H3;1H
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| Chemical Name |
2-(4-methoxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)phenoxy]-1-benzothiophen-6-ol , hydrochloride
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| Synonyms |
LY353381 HCl; LY353381; LY-353381; LY 353381; SERM3; Arzoxifene HCl; Arzoxifene hydrochloride.
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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 : ~25 mg/mL (~48.82 mM)
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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 | 1.9529 mL | 9.7645 mL | 19.5290 mL | |
| 5 mM | 0.3906 mL | 1.9529 mL | 3.9058 mL | |
| 10 mM | 0.1953 mL | 0.9764 mL | 1.9529 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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