GNE-274 is a structural analog of the ER degrading agent GDC-0927 and is a non-degrading agent. GNE-274 does not induce ER turnover in breast cancer cell lines and functions as a partial ER agonist. GNE-274 increases chromatin accessibility of ER-DNA binding sites, whereas GDC-0927 does not. GNE-274 is a potent ER ligand-binding domain (LBD) inhibitor. GNE-274 may be used in cancer research.

Physicochemical Properties

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)

Biological Activity

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].
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.
References	[1]. Therapeutic Ligands Antagonize Estrogen Receptor Function by Impairing Its Mobility. Cell. 2019 Aug 8;178(4):949-963.e18. [2]. Abstract NG05: Not all “SERDs” are equal: Context-independent ER degradation and full ER antagonism define the next generation of ER therapeutics. Cancer research.

Solubility Data

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.