| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
4‘-Hydroxytamoxifen TFA targets the estrogen receptor (ER), specifically ERalpha and ERbeta. As an active metabolite of tamoxifen, it is an ER antagonist (IC50 = 2.4 nM for the rabbit estrogen receptor). It acts as a selective estrogen receptor modulator (SERM), exhibiting mixed agonist/antagonist activity depending on the tissue context. It has a higher affinity for ER compared to tamoxifen itself. This compound induces non-apoptotic cytotoxicity in human endometrial adenocarcinoma cells.
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| ln Vitro |
In vitro, 4‘-Hydroxytamoxifen TFA has higher affinity for ER than tamoxifen itself. It induces non-apoptotic cytotoxicity in human endometrial adenocarcinoma cells (HEC-1A and HEC-1B). The compound may also exhibit estrogenic or antiestrogenic effects in various cell lines depending on the ER subtype and co-regulator expression. It is more potent than tamoxifen in ER binding assays. It has been used as a positive control in studies of tamoxifen metabolism and SERM pharmacology.
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| ln Vivo |
No specific in vivo efficacy data for the TFA salt itself are available. As the active metabolite of tamoxifen, 4‘-hydroxytamoxifen is responsible for much of tamoxifen's in vivo antitumor activity in breast cancer models. Orally administered tamoxifen is converted in the liver to 4‘-hydroxytamoxifen by CYP2D6 and other cytochrome P450 enzymes. The metabolite accumulates in target tissues and binds to ER with high affinity, blocking estrogen-driven tumor growth. No in vivo studies using directly administered 4'-Hydroxytamoxifen TFA have been described.
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| Enzyme Assay |
Competitive radioligand binding assay for ER: Uterine cytosol from ovariectomized rabbits or recombinant ER protein is incubated with 3H-estradiol (0.1-1 nM) and varying concentrations of 4'-Hydroxytamoxifen TFA (0.001-10 uM) in binding buffer (10 mM Tris-HCl, 1.5 mM EDTA, 0.2 mM PMSF, pH 7.4) for 16-24 hours at 4degC. Bound radioactivity is separated by dextran-coated charcoal adsorption. Non-specific binding is determined with 100-fold excess unlabeled diethylstilbestrol. IC50 values are calculated. For the metabolite, IC50 = 2.4 nM for rabbit ER.
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| Cell Assay |
Cell-based cytotoxicity assay: Human endometrial adenocarcinoma cells (HEC-1A or HEC-1B) are seeded in 96-well plates (5,000-10,000 cells/well) and incubated overnight. Cells are treated with varying concentrations of 4'-Hydroxytamoxifen TFA (0.01-100 uM) for 24-72 hours. Cell viability is measured by MTT, SRB (sulforhodamine B), or trypan blue exclusion. Apoptosis is assessed by Annexin V/PI flow cytometry and caspase-3 activity assays. For 4'-Hydroxytamoxifen TFA, non-apoptotic cytotoxicity (not mediated by caspase activation) was observed in HEC cells. ER-positive breast cancer cell lines (MCF-7, T47D) are also used to study ER antagonism.
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| Animal Protocol |
For xenograft models: female athymic nude mice (6-8 weeks old) are implanted subcutaneously with ER-positive MCF-7 breast cancer cells (5×10⁶ cells in Matrigel). When tumors reach approximately 100-200 mm3, mice are randomized into treatment groups. However, tamoxifen (the parent prodrug) is typically administered orally (5-50 mg/kg daily or every other day), not 4‘-hydroxytamoxifen itself, because the metabolite is less bioavailable. Tamoxifen is converted in vivo to 4'-hydroxytamoxifen via CYP2D6 and other P450 enzymes. For direct administration of 4‘-hydroxytamoxifen, intraperitoneal injection (1-10 mg/kg) using vehicle (e.g., 5% DMSO/30% PEG300/5% Tween 80/60% saline) can be used. Tumor size is measured every 2-3 days by calipers. After 3-4 weeks, tumors are excised, weighed, and analyzed for ER signaling markers (progesterone receptor, cyclin D1, etc.).
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| ADME/Pharmacokinetics |
Formal PK studies for the TFA salt are not available. As the active metabolite of tamoxifen, 4‘-hydroxytamoxifen has a longer half-life than the parent drug. It is extensively bound to plasma proteins (>99%) and accumulates in tissues. The TFA salt form is used as an analytical standard, not for in vivo dosing. For in vitro studies, the compound is soluble in DMSO and ethanol. Storage: powder at -20degC for up to 3 years, in solvent at -80degC for up to 1 year. Specific half-life, Cmax, and AUC values are not publicly available.
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| Toxicity/Toxicokinetics |
Comprehensive toxicity data for the TFA salt are not available. As an active metabolite of tamoxifen, it shares the toxicity profile of tamoxifen, which includes increased risks of endometrial cancer, venous thromboembolism, and hot flashes in clinical use. Endometrial adenocarcinoma cells show non-apoptotic cytotoxicity upon treatment with 4'-hydroxytamoxifen. Standard laboratory precautions for handling SERMs apply: use gloves and goggles, avoid inhalation. No specific LD50 or repeat-dose toxicity data are available.
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| References | |
| Additional Infomation |
4‘-Hydroxytamoxifen TFA is the TFA salt of the active metabolite of tamoxifen, a widely used SERM for breast cancer treatment and prevention. It exhibits higher ER affinity than tamoxifen and is used as an analytical standard in pharmacokinetic and metabolic studies of tamoxifen. It induces non-apoptotic cytotoxicity in endometrial cancer cells. The compound is for research use only and not intended for human therapy. No separate clinical trials or approvals exist beyond those of tamoxifen itself.
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| Molecular Formula |
C28H30F3NO4
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|---|---|
| Molecular Weight |
501.54
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| Appearance |
White to off-white solid powder
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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 : ~35 mg/mL (~69.79 mM; with ultrasonication)
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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 | 1.9939 mL | 9.9693 mL | 19.9386 mL | |
| 5 mM | 0.3988 mL | 1.9939 mL | 3.9877 mL | |
| 10 mM | 0.1994 mL | 0.9969 mL | 1.9939 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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