GNE-274

• CAT Number: I045263
• CAS Number: 2369048-69-9
• Molecular Formula: C29H31NO4
• Molecular Weight: 457.56
• Purity: ≥95%
• Synonyms: (2S)-3-(3-hydroxyphenyl)-4-methyl-2-[4-[(1-propylazetidin-3-yl)methoxy]phenyl]-2H-chromen-6-ol
• InChI: 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
• InChIKey: ABSGIUXAPWSTBC-LJAQVGFWSA-N
• SMILES: CCCN1CC(C1)COC2=CC=C(C=C2)C3C(=C(C4=C(O3)C=CC(=C4)O)C)C5=CC(=CC=C5)O

GNE-274 is a non-degrader that is structurally related to GDC-0927 (ER degrader). GNE-274 does not induce ER turnover and functions as a partial ER agonist in breast cancer cell lines. GNE-274 increase chromatin accessibility at ER-DNA binding sites, while GDC-0927 do not. GNE-274 is a potent inhibitor of ER-ligand binding domain (LBD). GNE-274 can be used for cancer research[1][2].
GNE-274 (0.1 nM-1000 nM; 4 hours) fails to trigger increased ER turnover in MCF7, MD-134, HCC1500 and CAMA cells[1].GNE-274 (1-1000 nM; 7-10 days) potently inhibits cellular proliferation, exhibiting greater potency than fulvestrant, 4-OHT, AZD9496, and GDC-0810 in E2-stimulated ER+ breast cancer cell lines[1].In transposaseaccessible chromatin sequencing (ATAC-seq) assay, GNE-274 increase chromatin accessibility at ER-DNA binding sites, it significantly alters chromatin accessibility at 594 sites. But GDC-0927 has considerably less impact on chromatin accessibility[1].

Reference

[1]. Jane Guan, et al. Therapeutic Ligands Antagonize Estrogen Receptor Function by Impairing Its Mobility. Cell. 2019 Aug 8;178(4):949-963.e18.
 [Content Brief]

[2]. Jane Guan, et al. Abstract NG05: Not all “SERDs” are equal: Context-independent ER degradation and full ER antagonism define the next generation of ER therapeutics. Cancer research.