Semaglutide (NN9535) is a synthetic, lipidated 31-residue analogue of human glucagon-like peptide-1, GLP-1(7–37). It carries two substitutions relative to the native sequence—α-aminoisobutyric acid (Aib) at position 8 and arginine at position 34 (GLP-1 numbering)—and Lys26 is acylated with octadecanedioic acid (C18 diacid) through a γ-glutamyl–bis(8-amino-3,6-dioxaoctanoyl) linker.

Semaglutide has been characterized as an agonist of the GLP-1 receptor (GLP-1R), a class B G protein-coupled receptor that signals predominantly through Gs and cAMP, with a reported GLP-1R affinity of 0.38 nM. The Aib8 substitution was introduced for stability against dipeptidyl peptidase-4 cleavage, and the C18 diacid side chain and linker mediate reversible, high-affinity binding to serum albumin. Cryo-EM structures of semaglutide-bound GLP-1R–Gs complexes show peptide interactions similar to native GLP-1, with distinct receptor and peptide dynamics.

Semaglutide is widely used as a reference GLP-1R agonist in receptor pharmacology and signalling studies, albumin-binding and peptide-stability research, structural biology of class B GPCRs, and LC-HRMS method development for lipidated peptides. Lyophilized material is hygroscopic and should be stored desiccated and protected from light.

Research use only. This material is sold for in-vitro laboratory research and development purposes exclusively. It is not a drug, food, or dietary supplement, has not been evaluated by the FDA, and must not be used in humans or animals.