GNE-274
Based on 1 Customer Validation
GNE-274 is a non-degrading estrogen receptor α (ERα/ESR1) modulator structurally similar to GDC-0927 (HY-111484). GNE-274 competes for binding to the ligand-binding domain of ERα and induces a coregulator-binding conformation similar to that of antagonists, yet retains partial agonistic transcriptional activity and does not promote ERα turnover. GNE-274 effectively inhibits E2-stimulated proliferation of ER-positive, HER2-negative breast cancer cells. GNE-274 promotes the recruitment of ERα to the nucleus and chromatin, increases chromatin accessibility, while largely maintaining the intranuclear mobility of ERα. GNE-274 can be used in research on ER-positive breast cancer and ERα transcriptional dynamics.
For research use only. We do not sell to patients.
- Purity: 98.00%
- CAS No.: 2369048-69-9
- Formula: C29H31NO4
- Molecular Weight:457.56
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Storage:
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
ERα |
In Vitro
GNE-274 competitively displaces the E2 fluorescent probe in a TR-FRET competitive binding assay using recombinant ERα ligand-binding domain, and displaces the E2-stimulated PGC1α peptide in a PGC1α coactivator binding assay, supporting that GNE-274 directly interacts with ERα LBD and induces an antagonist-like LBD conformation[1].
GNE-274 (4 h) does not induce increased ERα turnover or significant ERα degradation in the tested ER-positive breast cancer cells, acting as a non-degradative ERα ligand[1].
GNE-274 (1 nM E2; 7-10 d) effectively inhibits the cell viability/proliferation of ER-positive, HER2-negative breast cancer cells including MCF7, MDA-MB-134-VI, HCC1500, EFM-19, CAMA-1 and T-47D[1].
GNE-274 (1 μM; 24 h) downregulates 24% of E2-induced genes while upregulates 5% of them in MCF7 cells; it exhibits significant transcriptional agonist activity in HCC1500 cells, and displays transcriptional agonist characteristics to varying degrees in all tested ER-positive breast cancer cell lines[1].
GNE-274 (100 nM; 10 min-4 h) reduces the level of ERα in the cytoplasm of hormone-deprived MCF7 cells, while increasing ERα levels in the soluble nuclear and chromatin-enriched fractions, supporting that GNE-274 promotes ERα nuclear translocation and chromatin recruitment[1].
GNE-274 (100 nM; 45 min) induces the formation of 22,517 ERα chromatin-binding sites in MCF7 cells, which is a significant increase compared with the 4,413 sites in hormone-deprived controls, indicating that GNE-274 promotes the binding of ERα to chromatin[1].
GNE-274 (100 nM; 45 min) significantly alters 594 chromatin accessibility sites in MCF7 cells, with 85% of these sites showing increased accessibility; among the sites where GNE-274 induces ERα binding, 373 sites exhibit concurrent increases in chromatin accessibility[1].
GNE-274 stabilizes ERα in MCF7 cells with stable expression of mNeon-ERα, and maintains nuclear ERα mobility essentially similar to that of 4-OHT[1].
GNE-274 (100 nM; overnight) significantly reduces the proportion of Ki67-positive cells in mouse mammary epithelial explants cultured with LMx-Ag, and inhibits the ERα activity-associated gene expression signature as well as PGR expression, supporting its functional regulatory effect on the ERα pathway in intact mammary epithelial tissues[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF7
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Concentration:100 nM
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Incubation Time:10 min-4 h
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Result:Reduced cytoplasmic ERα and increased ERα in nuclear-soluble and chromatin-enriched fractions.
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Cell Line:MMEC explants
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Concentration:100 nM
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Incubation Time:overnight
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Result:Reduced PGR expression and supported suppression of ERα pathway activity.
Chemical Information
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CAS No. 2369048-69-9
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Appearance Solid
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Molecular Weight 457.56
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Formula C29H31NO4
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Color Off-white to light yellow
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SMILES
CCCN1CC(C1)COC2=CC=C([C@@H]3OC4=CC=C(C=C4C(C)=C3C5=CC(O)=CC=C5)O)C=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvent & Solubility
In Vitro:
DMSO : 200 mg/mL (437.10 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 1.75 mg/mL (3.82 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 1.75 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (17.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 1.75 mg/mL (3.82 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 1.75 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (17.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (285 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1855 mL | 10.9275 mL | 21.8551 mL | 54.6376 mL |
| 5 mM | 0.4371 mL | 2.1855 mL | 4.3710 mL | 10.9275 mL | |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1855 mL | 5.4638 mL | |
| 15 mM | 0.1457 mL | 0.7285 mL | 1.4570 mL | 3.6425 mL | |
| 20 mM | 0.1093 mL | 0.5464 mL | 1.0928 mL | 2.7319 mL | |
| 25 mM | 0.0874 mL | 0.4371 mL | 0.8742 mL | 2.1855 mL | |
| 30 mM | 0.0729 mL | 0.3643 mL | 0.7285 mL | 1.8213 mL | |
| 40 mM | 0.0546 mL | 0.2732 mL | 0.5464 mL | 1.3659 mL | |
| 50 mM | 0.0437 mL | 0.2186 mL | 0.4371 mL | 1.0928 mL | |
| 60 mM | 0.0364 mL | 0.1821 mL | 0.3643 mL | 0.9106 mL | |
| 80 mM | 0.0273 mL | 0.1366 mL | 0.2732 mL | 0.6830 mL | |
| 100 mM | 0.0219 mL | 0.1093 mL | 0.2186 mL | 0.5464 mL |
GNE-274 Related Classifications
HY-141551 Related Classifications
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