| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
| ln Vitro |
Endoxifen shows anti-estrogenic effects, and decreases the E2-induced PR expression in MCF-7 cells. Endoxifen also blocks ER-alpha transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation. In MCF7, HS 578T, and BT-549 cells, Endoxifen significantly inhibits cell proliferation. Endoxifen also exhibits four-fold higher inhibition on PKC activity compared to tamoxifen. Endoxifen inhibits the hERG current by preferentially interacting with the activated states of cloned hERG potassium channels with IC50 of 1.6 μM
Cell Assay: MCF7 and Ishikawa cells are grown in 10% triple charcoal-stripped serum-containing medium for 3 d. The cells are then plated at a density of 2,000 cells per well in 96-well tissue culture plates and treated as indicated every 48 h. Cell proliferation assays are conducted 8 days after the first treatment using a CellTiter-Glo Luminescent Cell Viability kit according to the manufacturers protocol. In MCF-7 human breast cancer cells, Endoxifen (10^-9 to 10^-6 M) dose-dependently inhibited E2 (10^-10 M)-induced progesterone receptor (PR) mRNA expression, with near-complete suppression at 10^-7 M (100 nM), a concentration close to therapeutic plasma levels (8-75 nM). Endoxifen alone (in the absence of E2) did not alter PR mRNA expression. The anti-estrogenic potency of Endoxifen was similar to that of 4-hydroxy-tamoxifen, and combination of both metabolites at 10^-7 M each did not show additive or antagonistic effects. No significant interconversion between Endoxifen and 4-hydroxy-tamoxifen was detected in the culture medium after 24 h.[1] |
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| ln Vivo |
In vivo, Endoxifen (8 mg/kg, ) inhibits growth of MCF-7 human mammary tumor xenografts in mice, showing more potency than Tamoxifen.
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| Cell Assay |
MCF-7 cells (estrogen receptor-positive human breast carcinoma cell line) were maintained at 37°C in 5% CO2 humidified atmosphere in improved minimum essential medium (IMEM) supplemented with 10% fetal bovine serum. Prior to experiments, cells were preconditioned in charcoal-stripped calf serum for 3 days to remove estrogens. Cells were treated with vehicle (0.1% ethanol), various doses of E2 (10^-13 to 10^-7 M), Endoxifen (10^-10 to 10^-6 M), 4-OH-Tam, or combinations for 24 h in IMEM with 10% charcoal-stripped calf serum. Total RNA was extracted from approximately 2.5×10^5 cells using an RNeasy Mini Kit, followed by DNase treatment. RNA concentration was measured by A260 and quality assessed by Agilent 2100 Bioanalyzer. cDNA was synthesized from DNase-treated total RNA using reverse transcription system. Real-time quantitative PCR (TaqMan) was performed using cDNA equivalent to 50 ng total RNA in an iCycler real-time PCR machine. PR and GAPDH were multiplexed. Primer and probe sequences for PR: forward 5'-GAG CAC TGG ATG CTG TTG CT-3', reverse 5'-GGC TTA GGG CTT GGC TTT C-3', probe 5'-FAM-TCC CAC AGC CAT TGG GCG TTC-BHQ1-3'. GAPDH: forward 5'-GAA GGT GAA GGT CGG AGT C-3', reverse 5'-GAA GAT GGT GAT GGG ATT TC-3', probe 5'-TxRed-CAA GCT TCC CGT TCT CAG CC-BHQ2-3'. Thermal cycling: 50°C for 2 min, 95°C for 2 min, then 42 cycles of 95°C for 15 s and 60°C for 1 min. Quantitative values from threshold cycle (Ct). Standard curve of PR single-stranded DNA showed good linear correlation. For measurement of metabolite interconversion, culture media were collected and concentrations of Endoxifen and 4-OH-Tam (Z- and E-isomers) were determined by HPLC with on-line derivatization and column switching. MCF-7 cells were treated with Endoxifen (10^-7 M), 4-OH-Tam (10^-7 M), or combination for 24 h in presence of E2 (10^-10 M), then media were analyzed.[1]
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| Animal Protocol |
Dissolved in water; 8 mg/kg; Oral gavage Mice bearing MCF-7 human mammary tumor xenografts
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| ADME/Pharmacokinetics |
In breast cancer patients receiving chronic tamoxifen (20 mg/day), average plasma concentration of Endoxifen is more than six-fold higher than that of 4-hydroxy-tamoxifen. Endoxifen plasma concentrations are highly variable and dependent on CYP2D6 genotype, with extensive metabolizers having up to 14-fold higher Endoxifen levels than 4-OH-Tam. The therapeutic plasma concentration range of Endoxifen in patients is approximately 8-75 nM. Endoxifen is formed from N-desmethyl-tamoxifen by CYP2D6, and its production is affected by CYP2D6 inhibitors and genetic polymorphisms.[1]
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| References |
Cancer Chemother Pharmacol.2005 May;55(5):471-8;Breast Cancer Res Treat.2010Jul;122(2):579-84.
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| Additional Infomation |
Endoxifen hydrochloride is the hydrochloride salt of endocifine and its cis (z-) stereoisomer, possessing potential antitumor activity. Endocifine is the active metabolite of tamoxifen, competitively inhibiting the binding of estradiol to estrogen receptors, thereby preventing the receptors from binding to estrogen-responsive elements on DNA and reducing DNA synthesis. However, unlike tamoxifen, which relies on CYP2D6 enzyme activity to convert to its active metabolite endocifine, directly administered endocifine bypasses the CYP2D6 pathway. Due to the significant inter-individual variability in CYP2D6 gene activity caused by CYP2D6 gene polymorphism, theoretically, endocifine is more potent and has more uniform bioavailability across different patient populations.
Endoxifen is an active metabolite of tamoxifen with anti-estrogenic properties. It is equipotent to 4-hydroxy-tamoxifen in suppressing E2-induced PR gene expression in breast cancer cells. Due to its higher plasma concentrations and comparable potency, Endoxifen is suggested to be more important than 4-hydroxy-tamoxifen for the anti-estrogenic action of tamoxifen in vivo. PR levels are routinely measured in breast cancer patients to guide tamoxifen therapy, and further clinical studies are needed to test the effects of CYP2D6 genetic variants on tamoxifen effectiveness related to Endoxifen concentrations.[1] |
| Molecular Formula |
C25H28CLNO2
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|---|---|---|
| Molecular Weight |
409.95
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| Exact Mass |
409.18
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| CAS # |
1032008-74-4
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| Related CAS # |
Endoxifen (Z-isomer);112093-28-4;Endoxifen hydrochloride;1197194-41-4;Endoxifen (E-isomer);114828-90-9;Endoxifen;110025-28-0;Endoxifen E-isomer hydrochloride;1197194-61-8
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| PubChem CID |
54613017
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| Appearance |
White to off-white solid powder
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| LogP |
6.552
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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 |
8
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| Heavy Atom Count |
29
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| Complexity |
467
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC/C(=C(\C1=CC=C(C=C1)O)/C2=CC=C(C=C2)OCCNC)/C3=CC=CC=C3.Cl
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| InChi Key |
RPFIMPDXTABYCN-BJFQDICYSA-
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| InChi Code |
InChI=1S/C25H27NO2.ClH/c1-3-24(19-7-5-4-6-8-19)25(20-9-13-22(27)14-10-20)21-11-15-23(16-12-21)28-18-17-26-2;/h4-16,26-27H,3,17-18H2,1-2H3;1H/b25-24-
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| Chemical Name |
(Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol hydrochloride
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.10 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4393 mL | 12.1966 mL | 24.3932 mL | |
| 5 mM | 0.4879 mL | 2.4393 mL | 4.8786 mL | |
| 10 mM | 0.2439 mL | 1.2197 mL | 2.4393 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03317405
Conditions:Breast Carcinoma In Situ|Breast Ductal Carcinoma In Situ|Breast Lobular Carcinoma In Situ|Stage I Breast Cancer AJCC v7|Stage IA Breast Cancer AJCC v7|Stage IB Breast Cancer AJCC v7|Stage II Breast Cancer AJCC v6 and v7|Stage IIA Breast Cancer AJCC v6 and v7|Stage IIB Breast Cancer AJCC v6 and v7|Stage III Breast Cancer AJCC v7|Stage IIIA Breast Cancer AJCC v7|Stage IIIB Breast Cancer AJCC v7|Stage IIIC Breast Cancer AJCC v7Link: https://clinicaltrials.gov/ct2/show/NCT02311933
Conditions:Recurrent Breast Carcinoma|Stage III Breast Cancer AJCC v7|Stage IIIA Breast Cancer AJCC v7|Stage IIIB Breast Cancer AJCC v7|Stage IIIC Breast Cancer AJCC v7|Stage IV Breast Cancer AJCC v6 and v7Link: https://clinicaltrials.gov/ct2/show/NCT01327781
Conditions:HER2/Neu Positive|Recurrent Breast Carcinoma|Stage IIIC Breast Cancer AJCC v7|Stage IV Breast Cancer AJCC v6 and v7Products are for research use only; We do not sell to patients
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