Research Library
Published research on this compound — for educational purposes only
How does GLP-G3 engage three receptor types simultaneously? (for educational purposes only)
GLP-G3 (LY3437943) is a single peptide engineered to activate GIP, GLP-1, and glucagon receptors through distinct structural domains within one alpha-helical chain. The peptide backbone incorporates sequence elements from all three native ligands, with the N-terminal region primarily driving glucagon and GLP-1 receptor activation and mid-chain residues contributing to GIP receptor engagement. A C-20 fatty diacid moiety enables albumin binding for extended half-life. In cell-based assays, GLP-G3 demonstrates agonist activity at all three receptors with engineered potency ratios. Research compound — not for human use.
Citation: Coskun T, Urva S, Roell WC, et al. “LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist for glycemic and metabolic endpoints.” Cell Metab. 2022;34(9):1234-1247.e9. PubMed
What does the glucagon receptor component contribute to GLP-G3’s pharmacology? (for educational purposes only)
The glucagon receptor (GCGR) agonist component distinguishes GLP-G3 from dual GIP/GLP-1 agonists. Glucagon receptor activation in preclinical models has been associated with increased hepatic lipid oxidation and elevated energy expenditure through thermogenic pathways. In cell-based assays, GLP-G3 activates GCGR-mediated cAMP signaling, engaging hepatic metabolic pathways distinct from those activated by GLP-1R or GIPR. The inclusion of GCGR agonism creates a pharmacological profile not achievable with mono- or dual-agonist compounds, engaging liver, pancreas, and adipose tissue receptor populations simultaneously. Research compound — not for human use.
Citation: Coskun T, Urva S, Roell WC, et al. “LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist for glycemic and metabolic endpoints.” Cell Metab. 2022;34(9):1234-1247.e9. PubMed
How does GLP-G3 compare structurally to dual agonists like GLP-2 T? (for educational purposes only)
While GLP-2 T engages two receptors (GIP and GLP-1), GLP-G3’s peptide sequence was engineered to additionally activate the glucagon receptor — requiring incorporation of glucagon-derived residues not present in dual agonist designs. Both compounds share lipidation strategies (C-20 fatty diacid for albumin binding) and DPP-4 resistance modifications, but GLP-G3’s sequence diverges substantially to accommodate three-receptor cross-reactivity within a single linear peptide. The structural challenge of maintaining potency at three distinct class B GPCRs simultaneously required extensive sequence optimization. Research compound — not for human use.
Citation: Coskun T, Urva S, Roell WC, et al. “LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist for glycemic and metabolic endpoints.” Cell Metab. 2022;34(9):1234-1247.e9. PubMed
What is GLP-G3’s receptor potency profile across GIP, GLP-1, and glucagon receptors? (for educational purposes only)
In vitro characterization demonstrates that GLP-G3 activates all three target receptors with distinct potency ratios. The compound shows highest relative potency at the GIP receptor, followed by GLP-1R, with moderate but pharmacologically relevant GCGR agonism. EC₅₀ values for cAMP accumulation at each receptor have been characterized in HEK293 cells expressing human receptors. The intentional potency imbalance — strongest at GIPR, intermediate at GLP-1R, and lowest at GCGR — was engineered to optimize the pharmacological profile while limiting potential glucagon-mediated glycogenolytic effects. Research compound — not for human use.
Citation: Coskun T, Urva S, Roell WC, et al. “LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist for glycemic and metabolic endpoints.” Cell Metab. 2022;34(9):1234-1247.e9. PubMed
Disclaimer: All research citations are provided for educational purposes only. These references describe findings from in vitro and animal model studies. This information does not constitute medical advice and should not be interpreted as endorsement of any specific application.