ICF GPR151 agonists for Irritable Bowel Syndrome

A chemical that switches on a mysterious gut nerve protein has been found, but it breaks down too fast in the liver to become a drug. This matters because the protein, GPR151, sits on nerves that control gut movement. When it malfunctions, it is linked to irritable bowel syndrome, diabetes, and chronic pain—conditions that affect millions of people and have few effective treatments. No one knows what naturally activates GPR151, making it an "orphan" target. The team screened 25,000 chemicals and tested around 200 variants to find a tool compound that measurably altered human gut muscle contractions. But that compound and its relatives are too insoluble and metabolically unstable for medicine. This grant funds a new approach: screening AstraZeneca’s chemical library against a cell-based assay for GPR151, aiming to find drug-like molecules that avoid the earlier problems. If successful, the researchers plan to spin out a company to fund the chemical synthesis and testing needed to turn a hit into a real treatment. The work is early-stage but directly targets a biological mechanism with clear relevance to gut disorders and pain.