G-36 is a cell-permeable G protein-coupled estrogen receptor (GPER/GPR30) antagonist that inhibits estrogen-mediated calcium mobilization (IC50=112nM)[1-2]. G-36 can be used in research on cancer-related signaling pathways[3-4].
In vitro, pretreatment of human umbilical vein endothelial cells (HUVECs) with G-36 (1μM) completely blocked the ethinylestradiol (EE) and estetrol (E4) (1nM–100nM)-induced cell migration and inhibited the accumulation of phosphorylated focal adhesion kinase at tyrosine 397 (FAK Y397)[5]. Treatment of human cervical squamous cell carcinoma (CSCC) cell lines SiHa and C33A with G-36 (1–5μM) for 3 to 7 days had no significant effect on cell migration, colony formation, or tumor spheroid formation; however, treatment of SiHa cells with 2.5μM G-36 significantly increased the protein expression of plasminogen activator inhibitor-1 (PAI-1)[6].
In vivo, G-36 (0.5mg/kg) was co-administered with G-1 via intraperitoneal injection to high-fat diet (HFD)-fed C57BL/6 male mice (5 times per week for 5 weeks). G-36 blocked the protective effects of G-1 against HFD-induced obese asthma, reversing G-1's effects on airway hyperresponsiveness (AHR), pulmonary immune cell infiltration, tissue inflammation, fibrosis, mucus hypersecretion, increases in pro-inflammatory M1 macrophages, and decreases in anti-inflammatory M2 macrophages[7]. In ovariectomized C57Bl6 female mice, a single subcutaneous injection of G-36 (50μg/kg) blocked the G-1 (10μg/kg)-induced proliferation of uterine epithelial cells and significantly reduced the 17β-estradiol (E2; 10μg/kg)-induced proliferation[8].
References:
[1] Meyer MR, Barton M. GPER blockers as Nox downregulators: A new drug class to target chronic non-communicable diseases. J Steroid Biochem Mol Biol. 2018 Feb;176:82-87.
[2] Yu X, Stallone JN, Heaps CL, et al. The activation of G protein-coupled estrogen receptor induces relaxation via cAMP as well as potentiates contraction via EGFR transactivation in porcine coronary arteries. PLoS One. 2018 Jan 23;13(1):e0191418.
[3] Sharma G, Mauvais-Jarvis F, Prossnitz ER. Roles of G protein-coupled estrogen receptor GPER in metabolic regulation. J Steroid Biochem Mol Biol. 2018 Feb;176:31-37.
[4] Evans PD. Rapid signalling responses via the G protein-coupled estrogen receptor, GPER, in a hippocampal cell line. Steroids. 2019 Dec;152:108487.
[5] Dama A, Baggio C, Trevisi L, et al. Regulation of human endothelial cell migration by oral contraceptive estrogen receptor ligands. Eur J Pharmacol. 2023 Apr 15;945:175591.
[6] Rörig L, Ruckriegl S, Gallwas J, et al. G Protein-coupled Estrogen Receptor 1 (GPER1) Regulates Expression of SERPINE1/PAI-1 and Inhibits Tumorigenic Potential of Cervical Squamous Cell Carcinoma Cells In Vitro. Cancer Genomics Proteomics. 2025 Jan-Feb;22(1):13-23.
[7] Son SE, Im DS. Activation of G Protein-Coupled Estrogen Receptor 1 (GPER) Attenuates Obesity-Induced Asthma by Switching M1 Macrophages to M2 Macrophages. Int J Mol Sci. 2024 Sep 2;25(17):9532.
[8] Dennis MK, Field AS, Burai R, et al. Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity. J Steroid Biochem Mol Biol. 2011 Nov;127(3-5):358-66.
G-36是一种具有细胞渗透性的G蛋白偶联雌激素受体（GPER/GPR30）拮抗剂，可抑制雌激素介导的钙动员（IC50=112nM）[1-2]。G-36可用于癌症相关的信号通路研究[3-4]。
在体外，G-36（1μM）预处理人脐静脉内皮细胞（HUVECs）6小时，可完全阻断由炔雌醇（EE）和雌四醇（E4）（1nM–100nM）所诱导的细胞迁移，并抑制磷酸化蛋白酪氨酸激酶2在酪氨酸397位点（FAK Y397）的积累[5]。G-36（1–5μM）处理人宫颈鳞状细胞癌（CSCC）细胞系SiHa和C33A细胞30至7天，对细胞的迁移能力、克隆形成以及肿瘤球形成均无显著影响；使用2.5μM G-36处理SiHa细胞，可显著增加其纤溶酶原激活物抑制剂-1（PAI-1）的蛋白表达[6]。
在体内，G-36（0.5mg/kg）与G-1共同腹腔注射处理高脂饮食（HFD）喂养的C57BL/6雄性小鼠（每周5次，持续5周）。G-36可阻断G-1对HFD诱导的肥胖性哮喘的保护作用，逆转G-1对气道高反应性（AHR）、肺部免疫细胞浸润、组织炎症、纤维化、粘液高分泌、促炎性M1巨噬细胞增多、抗炎性M2巨噬细胞减少[7]。G-36（50μg/kg；单次注射）通过皮下注射处理卵巢切除的C57Bl6雌性小鼠，可阻断G-1（10μg/kg）诱导的子宫上皮细胞增殖，并显著降低17β-雌二醇（E2；10μg/kg）诱导的增殖 [8]。