| Size | Price | Stock | Qty |
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| Targets |
4-Hydroxyestradiol targets DNA, forming adducts with purine bases. Its mechanism of action involves metabolic activation to reactive intermediates that can covalently bind to DNA. This DNA damage can lead to mutations and has been implicated in the carcinogenic effects of estrogens. The compound is a metabolite of estradiol, and its formation is catalyzed by CYP1B1. The estrogenic activity of 4-Hydroxyestradiol is lower than that of estradiol, but its ability to cause DNA damage is a key aspect of its biological profile.
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| ln Vitro |
In vitro, 4-Hydroxyestradiol has been shown to have carcinogenic and mutagenic activity in mammary epithelial cells. It forms adducts with adenine (N3) and guanine (N7) by depurinating sites in the DNA of cultured human breast epithelial cells. This DNA damaging activity is thought to contribute to the role of estrogen metabolites in the development of breast cancer. The compound is also an estrogen receptor agonist, but with lower potency than estradiol. Its in vitro activities include both estrogenic and genotoxic effects.
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| ln Vivo |
In vivo, 4-Hydroxyestradiol is a natural metabolite of estradiol. Its levels are influenced by the activity of CYP1B1, which catalyzes its formation. As a metabolite, it circulates in the blood and is present in various tissues. Its in vivo effects are a combination of its estrogenic activity and its ability to form DNA adducts. The balance between these activities and its conjugation and clearance pathways determine its overall biological impact. It has been implicated in the carcinogenic effects of estrogens in hormone-sensitive tissues.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for 4-Hydroxyestradiol typically involve studying its interaction with estrogen receptors or its metabolism by cytochrome P450 enzymes. A standard protocol for estrogen receptor binding: 4-Hydroxyestradiol is incubated with estrogen receptor alpha or beta in a buffer at 4°C for several hours. The binding affinity is measured by competitive displacement of a radiolabeled ligand, such as [³H]-estradiol, using scintillation counting or a fluorescence polarization assay. The IC50 or Ki value is calculated from the displacement curve. This assay measures the compound's ability to bind to and potentially activate the estrogen receptor.
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| Cell Assay |
In vitro cell-based assays for 4-Hydroxyestradiol typically assess its estrogenic activity and its genotoxic effects. A standard protocol for estrogenic activity: MCF-7 breast cancer cells are cultured in estrogen-free medium and treated with various concentrations of 4-Hydroxyestradiol for 48-72 hours. Cell proliferation is measured using the MTT or Alamar Blue assay. The compound's ability to stimulate cell growth is compared to that of estradiol. For genotoxicity, the compound's ability to induce DNA damage can be assessed using the comet assay or by measuring the formation of DNA adducts using mass spectrometry.
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| Animal Protocol |
In vivo animal experiments for 4-Hydroxyestradiol have been conducted to study its role in estrogen-induced carcinogenesis. A standard protocol: female rodents (e.g., rats or mice) are treated with 4-Hydroxyestradiol or a vehicle control by subcutaneous injection or oral gavage at various doses for a period of weeks to months. The animals are monitored for the development of tumors, particularly in hormone-sensitive tissues such as the mammary gland and uterus. At the end of the study, tissues are collected for histopathological examination and for analysis of DNA adducts. These studies have helped to establish the role of estrogen metabolites in carcinogenesis.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
4-Hydroxyestradiol is a known human metabolite of estradiol isomer and 17-β-estradiol. Pharmacokinetic properties of 4-Hydroxyestradiol are similar to those of other estrogens. It is a small lipophilic molecule (MW 288.38 g/mol) that is likely to be well-absorbed after oral administration. It circulates in the blood bound to sex hormone-binding globulin (SHBG) and albumin. Metabolism involves further hydroxylation, methylation, and conjugation (glucuronidation and sulfation), which facilitate its excretion. As an endogenous metabolite, its levels are tightly regulated by the balance between synthesis and clearance. |
| Toxicity/Toxicokinetics |
Toxicity of 4-Hydroxyestradiol is related to its carcinogenic and mutagenic activity. It forms DNA adducts that can lead to mutations, and it has been implicated in the development of breast and other cancers. The compound is also an estrogen receptor agonist, which can contribute to hormone-dependent tumor growth. Due to these toxic properties, it is classified as a potential carcinogen. Handling should be done with extreme caution using appropriate safety equipment to avoid exposure.
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| References |
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| Additional Infomation |
4-Hydroxy-17β-estradiol is a 4-hydroxy steroid formed by adding an extra hydroxyl group to the 4th carbon atom of 17β-estradiol. It is a metabolite functionally related to 17β-estradiol. 4-Hydroxyestradiol has been reported to exist in the human body, and relevant data exist. 4-Hydroxyestradiol is a metabolite formed during the metabolism of 17β-estradiol via hydroxylation of the 4th carbon atom by cytochrome P450 1B1, and it possesses potential carcinogenic activity. The pro-tumorigenic mechanism of 4-Hydroxyestradiol (4-OHE2) is not fully elucidated, but this metabolite undergoes a metabolic redox cycle with its oxidized quinone form—estradiol 3,4-quinone—producing reactive oxygen species (ROS), which in turn induce oxidative DNA damage. 4-OHE2 can also activate nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways, and stimulate the proliferation of susceptible cells by activating estrogen receptor (ER) to induce the expression of certain genes.
4-Hydroxyestradiol is an endogenous metabolite of estradiol formed by CYP1B1. It is a catechol estrogen with carcinogenic and mutagenic activity in mammary epithelial cells. It forms DNA adducts with adenine and guanine. The compound is used in research to study the mechanisms of estrogen-induced carcinogenesis. It is not a drug and has no therapeutic use. It is available from chemical suppliers for research purposes only. |
| Molecular Formula |
C18H24O3
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|---|---|
| Molecular Weight |
288.38136
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| Exact Mass |
288.173
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| CAS # |
5976-61-4
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| PubChem CID |
5282360
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| Appearance |
White to light yellow solid powder
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| Density |
1.248g/cm3
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| Boiling Point |
468.6ºC at 760 mmHg
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| Melting Point |
>210ºC (dec.)
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| Flash Point |
220.6ºC
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| Index of Refraction |
1.622
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| LogP |
3.314
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
21
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| Complexity |
411
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4O)O
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| InChi Key |
QOZFCKXEVSGWGS-ZHIYBZGJSA-N
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| InChi Code |
InChI=1S/C18H24O3/c1-18-9-8-11-10-4-6-15(19)17(21)13(10)3-2-12(11)14(18)5-7-16(18)20/h4,6,11-12,14,16,19-21H,2-3,5,7-9H2,1H3/t11-,12-,14+,16+,18+/m1/s1
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| Chemical Name |
(8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,4,17-triol
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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 | 3.4676 mL | 17.3382 mL | 34.6765 mL | |
| 5 mM | 0.6935 mL | 3.4676 mL | 6.9353 mL | |
| 10 mM | 0.3468 mL | 1.7338 mL | 3.4676 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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