Background:

G-15 is a selective antagonist of GPR30 with Ki value of 20 nM [1].

G protein-coupled receptor 30 (GPR30) is an integral membrane protein that localizes to the endoplasmic reticulum and with high affinity for estradiol and aldosterone. GPR30 participates in multiple intracellular signaling pathways [1].

G-15 is a selective GPR30 antagonist with Ki value of 20 nM, While displayed little binding to ERα or ERβ up to 10 μM. In SKBr3 breast cancer cells that expressed only GPR30, G-1 or estrogen significantly increased intracellular calcium concentrations, while G15 inhibited the response to G-1 or estrogen with IC50 value of 185 and 190 nM respectively in a dose-dependent way. In GPR30-transfected COS7 cells, G-15 inhibited both estrogen and G-1 activation of PI3K and accumulation of PIP3 [1]. In endometriotic cells, G-1 increased cell proliferation and Akt phosphorylation, while G-15 reversed this stimulation and inhibited cell proliferation and induced Akt dephosphorylation [2].

In intact rats and ovariectomized (OVX) rats treated with estradiol, G-15 impaired acquisition of delayed matching-to-position (DMP) T-maze task with a persistent turn. The result suggested that GPR30 played an crucial role in mediating the effects of estradiol on spatial learning [3].

参考文献:
[1].  Dennis MK, Burai R, Ramesh C, et al. In vivo effects of a GPR30 antagonist. Nat Chem Biol, 2009, 5(6): 421-427.
[2].  G-protein-coupled estrogen receptor and the GPER-antagonist G-15 inhibits proliferation in endometriotic cells. Fertil Steril, 2013, 100(3): 770-776.
[3].  Hammond R, Nelson D, Kline E, et al. Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats. Horm Behav, 2012, 62(4): 367-374.