Researchers at the University of New Mexico have recently characterized the novel G protein-coupled Estrogen Receptor (GPER) as a novel therapeutic target for obesity and diabetes (published in Science Translational Medicine volume 12, issue 528 on January 29, 2020).  They have patented unique compounds specific for binding GPER for use in treating disease states and conditions involving this receptor. The compounds of GPER-G-1 do not interact with the classical estrogen receptors (ERα/β), eliminating the typical feminizing effects of estrogen.  GPER-G-1 is focused on developing this proprietary technology into small molecule drug compounds, including G-1 (a GPER-selective agonist), and G15 and G36 (GPER-selective antagonists).  

The company’s leading drug candidate for the treatment of obesity (through weight loss) and the treatment of diabetes and pre-diabetes (by restoring insulin sensitivity and glucose homeostasis) is Tespria™, the GPER agonist G‑1.  In order to establish the therapeutic efficacy of this unique GPER-selective small molecule agonist, the UNM research team employed ovariectomy (removal of the ovaries) and high-fat diets to model the metabolic dysfunctions resulting from menopause (E2 deficiency) and naturally occurring obesity due to poor diet, respectively. Treatment of both female and male obese mice with Tespria significantly reduced body weight, decreased circulating cholesterol, increased energy expenditure, improved glucose tolerance and restored insulin sensitivity. The results demonstrate, for the first time, that GPER-selective agonism represents an innovative, safe and effective therapeutic approach for treating obesity and its associated metabolic disorders such as diabetes.