GPR151 agonists for Irritable Bowel Syndrome

GPR151 is an orphan protein - we do not know what activates it.

It is expressed in nerves and is associated with diseases involving altered gut motility such as irritable bowel syndrome, diabetes and pain.

Our team has discovered tool chemicals that activate the protein using UKRI funding to develop and validate suitable assays. We screened 25,000 diverse chemicals and found one that had activity.

We designed, made and tested around 200 closely related chemicals and developed a tool chemical that was used to show meaningful effects on human gut motility.

Unfortunately, the tool and related chemicals have issues with solubility and metabolic stability in the presence of liver enzymes. This makes them unsuitable for development into new medicines.

The aim of this grant is to find alternative chemicals that would be suitable for developing into medicines by screening AstraZeneca's collection against our cell-based assay of GPR151.

We aim to progress the project further by forming a company to provide the investment for the needed rounds of chemical synthesis and testing.