G-15 is a high-affinity, selective antagonist of G protein-coupled estrogen receptor (GPER/ GPR30) (Ki = 20nM) [1]. G‑15 competes with GPER for ligand binding sites, thereby blocking the action of hormones on the receptor, thereby inhibiting cell growth, proliferation or migration [2]. G‑15 is commonly used in cancer treatment research [3-4].
In SCC4, SCC9, and HSC-3 cells, after G-15 (5-20μM; 24h. 48h) treatment, all three cell lines showed dose-dependent inhibition of cell proliferation [5]. In MCF-7, MDA-MB-231, Bcap-37 cells, higher concentrations of G15 (1.25µM, 2.5µM, 5.0µM; 48h) significantly inhibited the viability of these three cell lines [6]. In A549 cells, G-15 (1μM; 24h) treatment inhibited cell growth [7].
In C57BL/6 mice, G-15 (50μg/kg; sc; 6d) treatment decreased expression of GPER in all treated age groups, with a significant decrease in mature animals [8]. In C57BL/6 mice, G-15 (10μg/kg, 50μg/kg; sc; 10d) treatment antagonizes the increase in striatal HVA/DA ratio induced by G1 [9].
References:
[1]. Kang W B, Cong Y, Ru J Y, et al. Osteoprotective effect of combination therapy of low-dose oestradiol with G15, a specific antagonist of GPR30/GPER in ovariectomy-induced osteoporotic rats[J]. Bioscience reports, 2015, 35(4): e00239.
[2]. Xu F, Ma J, Wang X, et al. The role of G protein-coupled estrogen receptor (GPER) in vascular pathology and physiology[J]. Biomolecules, 2023, 13(9): 1410.
[3]. Zhu Z, Nie X, Deng L, et al. Regulation of cervical cancer via G15-mediated inhibition of G protein-coupled estrogen receptor[J]. Anti-Cancer Drugs, 2024, 35(9): 817-829.
[4]. Liu C, Liao Y, Fan S, et al. G-protein-coupled estrogen receptor antagonist G15 decreases estrogen-induced development of non-small cell lung cancer[J]. Oncology Research, 2019, 27(3): 283.
[5]. Bai L Y, Weng J R, Hu J L, et al. G15, a GPR30 antagonist, induces apoptosis and autophagy in human oral squamous carcinoma cells[J]. Chemico-biological interactions, 2013, 206(2): 375-384.
[6]. Liu Y, Du F Y, Chen W, et al. G15 sensitizes epithelial breast cancer cells to doxorubicin by preventing epithelial-mesenchymal transition through inhibition of GPR30[J]. American Journal of Translational Research, 2015, 7(5): 967.
[7]. Shen Y, Li C, Zhou L, et al. G protein‐coupled oestrogen receptor promotes cell growth of non‐small cell lung cancer cells via YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 signalling[J]. Journal of cellular and molecular medicine, 2021, 25(1): 284-296.
[8]. Kotula-Balak M, Pawlicki P, Milon A, et al. The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation[J]. Cell and Tissue Research, 2018, 374(2): 389-412.
[9]. Bourque M, Morissette M, Côté M, et al. Implication of GPER1 in neuroprotection in a mouse model of Parkinson's disease[J]. Neurobiology of aging, 2013, 34(3): 887-901.
G-15是一种高亲和力、选择性的G蛋白偶联雌激素受体（GPER/ GPR30）拮抗剂（Ki = 20nM） [1]。G-15与GPER竞争配体结合位点，从而阻断激素对受体的作用，进而抑制细胞生长、增殖或迁移 [2]。G-15常用于癌症治疗研究 [3-4]。
在SCC4、SCC9和HSC-3细胞中，经G-15（5-20μM；24h，48h）处理后，这三种细胞系均表现出剂量依赖性的细胞增殖抑制 [5]。在 MCF-7、MDA-MB-231和Bcap-37细胞中，较高浓度的G15（1.25µM，2.5µM，5.0µM；48h）显著抑制了这三种细胞系的活力 [6]。在A549细胞中，G-15（1μM；24h）处理可抑制细胞生长 [7]。
在C57BL/6小鼠中，G-15（50μg/kg；sc；6d）处理降低了所有治疗年龄组的GPER表达，且在成熟小鼠中显著降低 [8]。在C57BL/6小鼠中，G-15（10μg/kg，50μg/kg；sc；10d）处理可拮抗G1诱导的纹状体HVA/DA比率的升高 [9]。