PEP20

PEP20 is a peptide-based agonist of the glucagon-like peptide-1 receptor (GLP-1R), specifically engineered to function as a biased agonist targeting the receptor's extracellular domain (ECD). Developed for the treatment of metabolic disorders, PEP20 was derived by fusing a 12-mer peptide (identified via high-throughput phage display screening) to the C-terminal sequence of Exendin-4 (residues 29–39), followed by the addition of a fatty acid chain modification to improve its pharmacokinetic profile and prolong its therapeutic half-life. Preclinical evaluation in diet-induced obesity (DIO) mouse models has demonstrated that PEP20 significantly reduces food intake and weight gain while exhibiting potent insulinotropic and glucose-lowering activities comparable to established GLP-1R agonists like liraglutide. Its biased signaling mechanism is intended to optimize metabolic control while potentially minimizing common gastrointestinal side effects associated with non-biased GLP-1R activation.

Other names

fatty chain-modified GLP-1 receptor agonistGLP-1R ECD-biased agonistGLP1R ECD-biased agonistGLP 1R ECD-biased agonist