I-14 (China Pharmaceutical University)

I-14 (also known as CPU014) is a preclinical small molecule agonist of the Free fatty acid receptor 1 (FFA1), also known as G protein-coupled receptor 40 (GPR40). Developed by researchers at China Pharmaceutical University, it is being investigated for the treatment of type 2 diabetes mellitus. The compound features an imidazo[1,2-a]pyridine core and was identified through structure-activity relationship studies based on a phenoxyacetic acid scaffold. By activating GPR40, which is highly expressed in pancreatic β-cells, I-14 stimulates insulin secretion in a glucose-dependent manner, potentially offering a lower risk of hypoglycemia compared to traditional insulin secretagogues. Preclinical studies in mouse models have demonstrated significant blood glucose-lowering effects and favorable pharmacokinetic properties. Notably, I-14 has shown a reduced risk of hepatotoxicity compared to earlier GPR40 agonists like TAK-875, positioning it as a promising candidate for further development.