GNE-274, a non-degrader compound structurally similar to GDC-0927 (an ER degrader), serves as a partial ER agonist in breast cancer cell lines without triggering ER turnover. Notably, GNE-274 enhances chromatin accessibility at ER-DNA binding sites, unlike GDC-0927. Acting as a potent inhibitor of the ER-ligand binding domain (LBD), GNE-274 exhibits potential for cancer research purposes.

GNE-274, at concentrations ranging from 0.1 nM to 1000 nM and applied over 4 hours, does not initiate increased ER turnover in MCF7, MB-134, HCC1500, and CAMA cells. However, when used at concentrations of 1-1000 nM for 7-10 days, it significantly suppresses cellular proliferation in E2-stimulated ER+ breast cancer cell lines, demonstrating superior efficacy compared to fulvestrant, 4-OHT, AZD9496, and GDC-0810. Additionally, GNE-274 enhances chromatin accessibility at ER-DNA binding sites in an ATAC-seq assay, altering accessibility at 594 sites distinctly, whereas GDC-0927 shows minimal impact. In a Cell Viability Assay involving various cell lines (MCF7, MB-134, HCC1500, EFM-19, CAMA-1, T-47D), with treatment concentrations from 1 nM to 1000 nM over 7-10 days, GNE-274 demonstrates IC 50 values roughly between 5nM to 20 nM, indicating its potency in inhibiting cell viability across different cells.