IUB447

IUB447 is a unimolecular peptide triagonist that simultaneously targets the receptors for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG). Developed as a therapeutic candidate for metabolic disorders, IUB447 aims to improve glycemic control and weight management. Mechanistically, it enhances glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells, a process primarily driven by its activity at the GLP-1 receptor and the subsequent activation of the Gαq protein and transient receptor potential melastatin 5 (TRPM5) signaling pathway. Preclinical studies in murine models have demonstrated that IUB447 provides superior insulinotropic effects compared to mono-agonist combinations and effectively manages metabolic phenotypes under high-fat diet conditions.