G-15

G-15は高親和性で、選択性のGタンパク質共役のエストロゲン受容体(GPER/ GPR30)の拮抗剤である(K_i = 20nM) ^[1]。リガンド結合部位を巡り、G-15はGPERと競合し、よって受容体でホルモンの行動を遮断することで、細胞の成長、増殖または遊離を阻害する^[2]。G-15は、癌治療の研究に広く使われている^[3-4]。

SCC4、SCC9とHSC-3細胞で、G-15 (5-20μM; 24h. 48h)の処理後、三つの細胞株とも、細胞増殖の用量依存的な阻害を示した^[5]。MCF-7、MDA-MB-231、Bcap-37細胞で、より高い濃度のG15 (1.25µM, 2.5µM, 5.0µM; 48h)は、これら三つの細胞株の生存率を著しく阻害した^[6]。A549細胞で、G-15 (1μM; 24h)の処理は、細胞の成長を阻害した^[7]。

C57BL/6マウスで、G-15 (50μg/kg; sc; 6d)の処理は、全ての治療年齢群で、GPERの発見を減らし、成体した動物では明らかに減少した^[8]。C57BL/6マウスで、G-15 (10μg/kg, 50μg/kg; sc; 10d)の処理は、線条体HVA/DA比で、G1による増加を拮抗する^[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.