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| 5mg |
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| Targets |
GW7604 is a potent antagonist of the Estrogen Receptor (ER), with activity against both ERalpha and ERbeta. It is the primary active metabolite responsible for the antiestrogenic effects of its parent compound, GW5638. By binding to ER, it blocks estrogen-driven transcriptional activation and cell growth.
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| ln Vitro |
In breast (MCF-7) and endometrial (ECC-1) cell lines, GW7604 is the putative metabolite of GW5638. The induction of TGF-alpha in MDA-MB-231 cells is inhibited by GW7604 (0.1 nM-1 μM; 24 hours) in a concentration-related manner, in comparison to the effects of estradiol (1 nM) and 4-hydroxytamoxifen (4-OHT; 10 and 100 nM)[1].
GW7604 is the presumed metabolite of GW5638 in breast (MCF-7) and endometrial (ECC-1) cell lines. It inhibits both 17beta-estradiol (1 nM) and 4-hydroxytamoxifen (4-OHT; 10 and 100 nM) induction of TGF-alpha in a concentration-dependent manner (0.1 nM-1 microM). It blocks the effect of estradiol (E2; 1 nM) in a concentration-related manner. |
| ln Vivo |
As the active metabolite of GW5638, GW7604 is the primary driver of the parent compound's antitumor activity in vivo. It is being researched for its ability to overcome tamoxifen resistance in ER+ breast cancer models, offering a different pharmacological profile than current SERMs and SERDs.
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| Enzyme Assay |
Cell-free ER binding assays are performed using a radioligand competition format. Purified ERalpha or ERbeta is incubated with radiolabeled 17beta-estradiol (3H-E2) and varying concentrations of GW7604 at 4degC for 12-16 hours. The bound and free ligands are separated by charcoal adsorption or filtration. The half-maximal inhibitory concentration (IC50) is determined via scintillation counting.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-231 cells Tested Concentrations: 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Blocked the effect of estradiol (E2; 1 n M) in a concentration-related manner. MDA-MB-231 breast cancer cells (which can be transfected to express ER) or MCF-7 cells are used. Cells are serum-starved and then treated with 1 nM 17beta-estradiol (E2) in the presence or absence of a dilution series of GW7604 for 24 hours. The activity is measured by quantifying the protein levels of an E2-responsive gene, such as TGF-alpha, via Western blot analysis. |
| Animal Protocol |
The in vivo efficacy of GW5638, whose active metabolite is GW7604, is evaluated in ovariectomized athymic mice bearing ER+ MCF-7 xenograft tumors. Mice are treated with GW5638 (via oral gavage or subcutaneous injection) for several weeks. Tumor growth inhibition (TGI) is monitored with calipers. The study aims to demonstrate the compound's ability to suppress estrogen-dependent tumor growth and its potential to overcome tamoxifen resistance.
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| ADME/Pharmacokinetics |
GW7604 is the active metabolite, and its parent compound, GW5638, is characterized by significant oral bioavailability. GW5638 is a prodrug that is rapidly converted to GW7604 in vivo, resulting in sustained systemic exposure to the active antiestrogen. This pharmacokinetic property is crucial for its potential as an oral therapeutic.
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| Toxicity/Toxicokinetics |
Toxicological studies for GW7604 are tied to its parent compound, GW5638. Preclinical evaluations have focused on its antiestrogenic effects on reproductive tissues, such as the uterus. As a pure antagonist, it does not exhibit the partial agonist activity seen with tamoxifen, suggesting a potentially favorable toxicity profile in terms of endometrial safety.
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| References | |
| Additional Infomation |
GW7604 is the active metabolite of GW5638, a clinically relevant antiestrogen. Research on GW7604 has helped elucidate the molecular mechanisms of action of this new class of ER antagonists. It serves as a structural and pharmacological reference for developing next-generation SERDs to treat ER+ breast cancer, particularly in patients who have acquired resistance to tamoxifen.
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| Molecular Formula |
C25H22O3
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| Molecular Weight |
370.440387248993
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| Exact Mass |
370.156
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| CAS # |
361203-06-7
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| PubChem CID |
46885714
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| Appearance |
White to off-white solid powder
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
554
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC/C(=C(\C1=CC=C(C=C1)/C=C/C(=O)O)/C2=CC=C(C=C2)O)/C3=CC=CC=C3
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| InChi Key |
SCVIEONTACSLJA-VZBZSUMNSA-N
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| InChi Code |
InChI=1S/C25H22O3/c1-2-23(19-6-4-3-5-7-19)25(21-13-15-22(26)16-14-21)20-11-8-18(9-12-20)10-17-24(27)28/h3-17,26H,2H2,1H3,(H,27,28)/b17-10+,25-23-
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| Chemical Name |
(E)-3-[4-[(Z)-1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenyl]prop-2-enoic acid
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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 | 2.6995 mL | 13.4975 mL | 26.9949 mL | |
| 5 mM | 0.5399 mL | 2.6995 mL | 5.3990 mL | |
| 10 mM | 0.2699 mL | 1.3497 mL | 2.6995 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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