Semaglutide

Semaglutide is a synthetic long-acting GLP-1 receptor agonist based on native GLP-1(7-37) with three key structural modifications that collectively extend its plasma half-life to approximately 7 days. Aib substitution at position 8 blocks DPP-IV cleavage — the primary route of GLP-1 inactivation. Arg34 substitution replaces Lys34 to eliminate an unwanted secondary fatty acid attachment site. A C18 fatty diacid chain at Lys26 enables high-affinity non-covalent albumin binding for extended circulation.

Molecular formula: C187H291N45O59 | Molecular weight: 4113.58 g/mol | CAS: 910463-68-2 | Drug class: GLP-1R monoagonist | Half-life: approximately 7 days | Purity: greater than or equal to 98% as verified by HPLC | Form: Lyophilised powder | Appearance: White to off-white lyophilised powder | Storage: -20°C desiccated

As the standard GLP-1R monoagonist reference compound, Semaglutide is central to comparative incretin pharmacology research. GLP-1R activation (via Gs/cAMP/PKA) stimulates glucose-dependent insulin secretion in pancreatic beta cell models, suppresses appetite through hypothalamic GLP-1R signalling, and delays gastric emptying via peripheral GLP-1R. Semaglutide demonstrates balanced (non-biased) GLP-1R agonism, activating both G-protein and beta-arrestin pathways — contrasting with Tirzepatide's GLP-1R bias and enabling mechanistic comparison research.

Published characterisation by Lau et al. (Journal of Medicinal Chemistry, 2015) described the structural design rationale. Drucker (Cell Metabolism, 2018) reviewed GLP-1R mechanism comprehensively. Used as the reference GLP-1R monoagonist alongside Tirzepatide (dual GLP-1R/GIPR) and Retatrutide (triple GLP-1R/GIPR/GCGR) in comparative incretin research.

Supplied as a lyophilised powder. Reconstitute with bacteriostatic water. Store at -20°C. For laboratory and analytical research purposes only. Not for human or veterinary use.