A Series of Indole-Thiazole Derivatives Act as GPER Agonists and Inhibit Breast Cancer Cell Growth

The G protein-coupled estrogen receptor (GPER, GPR30) represents a promising target for the treatment of estrogen receptor alpha and beta negative breast cancers. Previously reported agonists of GPER have shown that activation of GPER inhibits breast cancer cell proliferation. We report herein a new GPER agonist scaffold based upon in silico pharmacophore screening. Three of these compounds were found to increase cAMP at similar levels as the known GPER-selective agonist G-1. Compound 5 was found to be selective for GPER (over estrogen receptor alpha and beta) and inhibit breast cancer cell proliferation at levels consistent with G-1. Docking studies go on to suggest that both 5 and G-1 bind within the same binding pocket in GPER and point to possible key residues that are important in GPER activation.