exendin-4-C16

Exendin-4-C16 is a C-terminally acylated analog of exendin-4, in which a palmitic acid (C16 diacid) is conjugated to the peptide’s C-terminus via a GK (glycine-lysine) linker. Exendin-4 is a 39-amino acid peptide that acts as a potent agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulating insulin secretion, suppressing glucagon release, and lowering blood glucose. The C16 acyl modification enhances albumin binding, leading to prolonged pharmacokinetics and improved duration of glucose lowering, with activity lasting up to 72 hours in mice. Unique to exendin-4-C16 is biased agonism: it shows increased preference for G protein recruitment over β-arrestin-2, resulting in enhanced insulinotropic efficacy and reduced receptor desensitization. It is primarily being explored as a long-acting GLP-1 receptor agonist for metabolic diseases such as type 2 diabetes and obesity[2][3].