| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| 25mg | |||
| Other Sizes |
| Targets |
Estrogen Receptor alpha/beta (ERalpha/ERbeta); Hsp90 Molecular Chaperone. Tamoxifen-d5 acts as a mixed agonist/antagonist of estrogen receptors in a tissue-dependent manner. It is an antagonist in breast tissue (blocking estrogen-driven proliferation) and an agonist in bone, uterus, and the cardiovascular system. Tamoxifen is also a potent activator of Hsp90, enhancing its ATPase activity and molecular chaperone function.
|
|---|---|
| ln Vitro |
Tamoxifen binds to rabbit estrogen receptor with an IC50 of 45 nM. It reduces the proliferation of MCF-7 human breast cancer cells with an IC50 of approximately 10 microM in vitro. The active metabolite, 4-hydroxytamoxifen, has 100-fold higher affinity for ER (IC50 ~0.5-1 nM). Tamoxifen also inhibits protein kinase C (PKC) activity and induces apoptosis in ER-positive breast cancer cells.
|
| ln Vivo |
In athymic nude mice bearing MCF-7 breast cancer xenografts, oral or subcutaneous administration of tamoxifen (50-100 microg/day for 21 days) significantly reduces tumor volume (by 40-70%) compared to vehicle controls. In the rat uterus, tamoxifen induces an estrogen-like increase in uterine weight and luminal epithelial height, demonstrating its partial agonist activity in the reproductive tract.
|
| Enzyme Assay |
Tamoxifen binding to estrogen receptors is assessed by radioligand binding assays. Rabbit uterine cytosol or recombinant human ERalpha/ERbeta is used as the receptor source. Cytosol (100-200 microg protein) is incubated with [3H]estradiol (1-2 nM) and varying concentrations of tamoxifen-d5 in TE buffer (10 mM Tris, 1.5 mM EDTA, pH 7.4) for 18-20 hours at 4degC. Unbound and bound radioligands are separated by dextran-coated charcoal adsorption, and bound radioactivity is measured in the supernatant by liquid scintillation counting. IC50 values are determined and Ki values calculated using the Cheng-Prusoff equation.
|
| Cell Assay |
MCF-7 human breast cancer cells are cultured in DMEM/F12 medium supplemented with 10% FBS and 1% penicillin/streptomycin. For proliferation assays, cells are seeded in 96-well plates (5,000 cells/well) in phenol red-free medium with 10% charcoal-stripped FBS. After 24 hours, varying concentrations of tamoxifen-d5 (0.01-100 microM) are added, and cells are incubated for 3-7 days. Cell viability is measured using the MTT assay (absorbance at 570 nm) or CellTiter-Glo (luminescence). The IC50 for proliferation inhibition is calculated from dose-response curves. Apoptosis is assessed by flow cytometry using Annexin V-FITC/PI double staining.
|
| Animal Protocol |
Female athymic nude mice (5-6 weeks old, 18-22 g) are bilaterally ovariectomized and implanted subcutaneously with 0.72 mg 17beta-estradiol pellets to provide systemic estrogen. After 3 days, MCF-7 cells (5 × 10⁶ in 50% Matrigel) are injected subcutaneously into the flank. When tumors reach approximately 100-150 mm3 (10-14 days), mice are randomized into treatment groups (n=8-10). Tamoxifen citrate (50-100 microg/day) or tamoxifen-d5 (50-100 microg/day) is administered subcutaneously or orally daily for 21 days. Tumor volumes are measured twice weekly with calipers. Tumor growth inhibition (TGI) and final tumor weights are calculated. Plasma is collected for LC-MS/MS quantification of drug levels.
|
| ADME/Pharmacokinetics |
Tamoxifen-d5 serves as an internal standard for LC-MS/MS bioanalysis of tamoxifen. The parent drug tamoxifen is well absorbed orally (bioavailability ~80%), with a long half-life of 5-7 days due to enterohepatic recirculation and extensive distribution. It is >99% protein bound and is metabolized by CYP3A4, CYP2D6, and CYP2C9 to active metabolites, including 4-hydroxytamoxifen and endoxifen (which has 100-fold higher ER binding affinity). Tamoxifen is a potent CYP3A4 inducer.
|
| Toxicity/Toxicokinetics |
Tamoxifen is generally well tolerated but has a unique safety profile due to its SERM properties. Common side effects include hot flashes (50-80%), vaginal discharge, nausea, and fatigue. Serious adverse effects include increased risk of endometrial cancer (2-3 fold) and venous thromboembolism (DVT/PE). Rare side effects include stroke, pulmonary embolism, and cataracts. Tamoxifen causes teratogenicity in animals and is pregnancy category D.
|
| References | |
| Additional Infomation |
Tamoxifen (Nolvadex®, Soltamox®) was FDA-approved in 1977 for the treatment of ER-positive breast cancer and remains the gold standard for adjuvant endocrine therapy in premenopausal women. It is also approved for risk reduction in high-risk women. The D5-labeled version is a research internal standard used extensively in clinical pharmacology, therapeutic drug monitoring, drug-drug interaction studies, and analytical method development for tamoxifen and its metabolites in biological samples.
|
| Molecular Formula |
C26H29NO
|
|---|---|
| Molecular Weight |
371.51456
|
| Exact Mass |
376.256
|
| CAS # |
157698-32-3
|
| Related CAS # |
Tamoxifen Citrate;54965-24-1;Tamoxifen;10540-29-1
|
| PubChem CID |
3036736
|
| Appearance |
White to off-white solid powder
|
| Density |
1.057g/cm3
|
| Boiling Point |
482.3ºC at 760mmHg
|
| Flash Point |
140ºC
|
| Vapour Pressure |
1.85E-09mmHg at 25°C
|
| Index of Refraction |
1.582
|
| LogP |
5.996
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
28
|
| Complexity |
463
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[2H]C([2H])([2H])C([2H])([2H])/C(=C(\C1=CC=CC=C1)/C2=CC=C(C=C2)OCCN(C)C)/C3=CC=CC=C3
|
| InChi Key |
NKANXQFJJICGDU-FUYVPVGLSA-N
|
| InChi Code |
InChI=1S/C26H29NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18H,4,19-20H2,1-3H3/b26-25-/i1D3,4D2
|
| Chemical Name |
N,N-dimethyl-2-[4-[(Z)-3,3,4,4,4-pentadeuterio-1,2-diphenylbut-1-enyl]phenoxy]ethanamine
|
| 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 |
| 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 : ~83.33 mg/mL (~221.30 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 | 2.6917 mL | 13.4586 mL | 26.9172 mL | |
| 5 mM | 0.5383 mL | 2.6917 mL | 5.3834 mL | |
| 10 mM | 0.2692 mL | 1.3459 mL | 2.6917 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
