GNE-274 是 ER 降解剂 GDC-0927 的结构类似物，是一种非降解剂。GNE-274 在乳腺癌细胞系中不诱导 ER 的转换，作为 ER 的部分激动剂 (partial ER agonist) 发挥作用。GNE-274 增加了ER-DNA 结合位点的的染色质可进入性，而 GDC-0927 则没有。GNE-274 是一种有效的 ER 配体结合域 (LBD) 抑制剂。GNE-274 可用于癌症研究。
货号:ajcx39908
CAS:2369048-69-9
分子式:C29H31NO4
分子量：457.56
溶解度:N/A
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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