Mazdutide

Mazdutide is a novel long-acting dual glucagon-like peptide-1 (GLP-1) receptor and glucagon receptor (GCGR) agonist. Mazdutide potently activates the GLP-1R signaling pathway to stimulate glucose-dependent insulin secretion through activity at the GCG receptor (GCGR) or the GLP-1R. Mazdutide is a synthetic peptide analog of the gut peptide hormone oxyntomodulin that reduces body weight in both Gcgr-/- and Glp1r-/- mice. Mazdutide binds human and mouse GCGR (Ki: 17.7nM and 15.9nM, respectively) and GLP-1R (Ki: 28.6nM and 25.1nM, respectively) and stimulates insulin secretion from mouse islets (EC50: 5.2 nM). Mazdutide is used in studies of obesity and type 2 diabetes (T2D) and is designed enhancing energy expenditure and fat metabolism. Mazdutide comprises a 33 amino acid linear synthetic peptide conjugated to a C20 fatty diacid moiety through a hydrophilic linker at the lysine residue at position 20. Due to this moiety, the compound is highly bound to albumin in the plasma which prolongs its half-life. It contains one non-coded amino acid residue (Aib, alpha-amino isobutyric acid) at position 2.