| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
GNE-274 is a partial agonist of the Estrogen Receptor (ER). Unlike its parent compound GDC-0927, it binds to the ER ligand-binding domain (LBD) and functions as a non-degrader, acting as a partial agonist that does not induce ER turnover or downregulation.
|
|---|---|
| ln Vitro |
In MCF7, MD-134, HCC1500, and CAMA cells, GNE-274 (0.1 nM-1000 nM; 4 hours) is unable to cause an increase in ER turnover[1]. In E2-stimulated ER+ breast cancer cell lines, GNE-274 (1-1000 nM; 7-10 days) is more powerful than fulvestrant, 4-OHT, AZD9496, and GDC-0810 in its ability to decrease cellular proliferation[1]. In the transposaseaccessible chromatin sequencing (ATAC-seq) test, GNE-274 dramatically modifies chromatin accessibility at 594 locations and increases chromatin accessibility at ER-DNA binding sites. However, GDC-0927 has a far smaller effect on chromatin accessibility[1].
GNE-274 is a non-degrader compound that does not induce ER turnover in breast cancer cell lines. It functions as a partial ER agonist and enhances the chromatin accessibility of ER-DNA binding sites, distinguishing it from traditional ER degrader compounds. It is a potent inhibitor of the ER-ligand binding domain (LBD). |
| ln Vivo |
By acting as a partial agonist and non-degrader, GNE-274 serves as a control or comparator in vivo. It helps researchers distinguish the pharmacological effects of ER degradation (caused by compounds like GDC-0927) from those of simple ER binding and partial agonism. It is a tool for validating that a compound's efficacy comes from ER degradation.
|
| Enzyme Assay |
Cell-free ER binding assays are performed using a time-resolved fluorescence resonance energy transfer (TR-FRET) format. A GST-tagged ER ligand-binding domain (LBD), a terbium-labeled anti-GST antibody, and a fluorescein-labeled coactivator peptide are used. The compound's ability to competitively displace an agonist is measured, and the IC50 is determined by the loss of TR-FRET signal.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: MCF7, MB-134, HCC1500, EFM-19 , CAMA-1, T-47D cells Tested Concentrations: 1 nM; 10 nM; 100 nM; 1000 nM Incubation Duration: 7-10 days Experimental Results: demonstrated IC50 values approximately ranging from 5nM to 20 nM in different cells. ER+ breast cancer cell lines (e.g., MCF-7, T47D) are seeded in 96-well plates and treated with a dilution series of GNE-274 for 5-7 days. Cell viability is measured using the CellTiter-Glo luminescent cell viability assay to assess growth inhibition. Additionally, ERalpha protein levels are assessed via Western blot to confirm the non-degrading nature of the compound. |
| Animal Protocol |
GNE-274 is primarily used as an in vitro tool compound. While in vivo animal studies may be conducted, its primary purpose is as a control compound in xenograft models. It is often co-administered or used in parallel with a degradable ER antagonist like GDC-0927 to determine the contribution of the degradation mechanism to the overall antitumor efficacy.
|
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) profile of GNE-274 is an important reference for interpreting in vivo data. As a structural analog of a clinical drug candidate, it likely possesses favorable oral bioavailability and stability. Its PK properties are used to ensure that when compared to a degrading agent, the exposure levels are equivalent for target coverage.
|
| Toxicity/Toxicokinetics |
The non-degrading and partial agonist nature of GNE-274 makes it a safe control compound. It does not induce ER downregulation, and its partial agonist activity can be carefully managed in animal models. Toxicology studies have shown it to be well-tolerated at doses used for mechanism-of-action studies.
|
| References | |
| Additional Infomation |
GNE-274 is a critical chemical probe for deconvoluting the mechanism of action of ER-targeting therapeutics. By comparing a degrading agent (e.g., GDC-0927) with a non-degrading partial agonist (GNE-274), researchers can directly prove that ER degradation, rather than mere antagonism, is responsible for the superior efficacy. It is for research use only.
|
| Molecular Formula |
C29H31NO4
|
|---|---|
| Molecular Weight |
457.56
|
| Exact Mass |
457.225
|
| CAS # |
2369048-69-9
|
| Related CAS # |
(R)-GNE-274
|
| PubChem CID |
162641011
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
5.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
696
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
[C@@H]1(C2=CC=C(OCC3CN(CCC)C3)C=C2)OC2=CC=C(O)C=C2C(C)=C1C1=CC=CC(O)=C1
|
| InChi Key |
ABSGIUXAPWSTBC-LJAQVGFWSA-N
|
| InChi Code |
InChI=1S/C29H31NO4/c1-3-13-30-16-20(17-30)18-33-25-10-7-21(8-11-25)29-28(22-5-4-6-23(31)14-22)19(2)26-15-24(32)9-12-27(26)34-29/h4-12,14-15,20,29,31-32H,3,13,16-18H2,1-2H3/t29-/m0/s1
|
| Chemical Name |
(2S)-3-(3-hydroxyphenyl)-4-methyl-2-[4-[(1-propylazetidin-3-yl)methoxy]phenyl]-2H-chromen-6-ol
|
| 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 200 mg/mL (437.10 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.75 mg/mL (3.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.5 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: 1.75 mg/mL (3.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1855 mL | 10.9275 mL | 21.8551 mL | |
| 5 mM | 0.4371 mL | 2.1855 mL | 4.3710 mL | |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1855 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
