Insights into the pharmacology of GPER/GPR30 and its involvement in gallstone formation

Abstract

The prevalence of gallstone disease is a major public health issue globally, and due to complex etiology of gallstones, there are a limited number of pharmaceuticals available. While the G protein‐coupled estrogen receptor (GPR30/GPER) has been shown to induce gallstone formation, little is known about its chemical biology and pharmacology. Building upon previous computational modeling of GPER, a novel series of antagonists were designed and synthesized. These novel compounds were assessed for their therapeutic value via calcium mobilization, cyclic AMP, and estrogen receptor a and β binding assays. From this series of compounds, one compound, SG‐1, exhibited superior antagonism and selectivity for GPER. The potential therapeutic value of SG‐1 was further validated in an in vivo mouse model of gallstone formation. Data revealed that SG‐1 treatment results in a dose‐dependent reduction in gallstone prevalence in estrogen‐treated ovariectomized mice.Support or Funding InformationSupported by startup funds from Saint Louis University (C.A.) and this work was supported in part by research grants DK73917 and DK101793 (to D.W.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.