AlphaMol Presents Oral GPR75 Discovery Strategy at ObesityWeek 2026

AlphaMol Co-Founder Dr. Shuguang Yuan presented the scientific rationale for developing oral small-molecule antagonists of GPR75 at ObesityWeek 2026, currently taking place in the Washington, D.C., area. The presentation connected human genetics, tissue-specific functional studies and structure-informed drug discovery to explore a peripherally restricted approach to obesity and associated metabolic diseases. GPR75 has emerged as a potential obesity drug target following large-scale human genetic studies linking loss-of-function variants to lower body mass index and reduced odds of obesity. Animal studies have provided further support, showing that Gpr75 deficiency can limit high-fat-diet-induced weight gain, reduce adiposity and improve selected measures of liver metabolism. The presentation examined the distinct contributions of neural and peripheral GPR75 biology. Existing research supports a role for neural GPR75 in food intake and energy balance. However, these genetic findings do not directly establish whether a therapeutic antagonist must enter the brain. Studies in hepatocytes and adipocytes also provide a rationale for peripheral intervention, although adipocyte findings vary with sex and experimental model. Against this background, AlphaMol outlined a discovery strategy focused on peripherally restricted GPR75 inverse agonist. The approach seeks to control brain exposure through molecular design while testing whether peripheral inhibition can deliver meaningful effects on body weight and metabolic health. Its potential efficacy and long-term safety require further experimental and clinical validation. The presentation illustrated AlphaMol’s approach to connecting human genetic evidence with GPCR mechanisms and structure-informed molecular design, providing a framework for evaluating the translational potential of GPR75 inhibition. ObesityWeek 2026 runs November 14–17, bringing together researchers and healthcare professionals working across obesity science, clinical care and translational medicine.