Overview
BI-456906-S is a research-grade reference compound within the dual glucagon receptor and GLP-1 receptor co-agonist class. Chemically characterized as a 29-amino-acid synthetic peptide incorporating structural elements of both glucagon and GLP-1, with a C18 fatty-acid side chain for extended half-life, the compound has been studied in preclinical and clinical research for its role in dual-receptor pharmacology and metabolic pathway biology distinct from GLP-1-only or GIP/GLP-1 dual agonists (Zimmermann et al., 2022 — PMID: 35134357).
History
The survodutide class emerged from research efforts to combine GLP-1 receptor agonism with glucagon receptor agonism in a single molecule, investigating whether the addition of glucagon receptor activation could produce complementary pharmacodynamic effects compared to GLP-1-only or GIP/GLP-1 dual agonists. Research has characterized the compound’s balanced activity at both receptors, with particular focus on hepatic fat oxidation and energy expenditure pathways mediated through glucagon receptor engagement (Le Roux et al., 2024).
Structure & Molecular Data
| CAS Number | 2230867-66-2 |
| Molecular Formula | C₁₈₆H₂₈₅N₄₅O₅₆ |
| Molecular Weight | 4,092.61 g/mol |
| Amino Acid Count / Structure | 29-amino-acid dual receptor co-agonist peptide |
| PubChem CID | 157007878 |
| Sequence | 29-residue synthetic peptide engineered for balanced activity at GLP-1 and glucagon receptors with C18 fatty-acid side chain for albumin binding |
| Appearance | Lyophilized white powder |
| Storage | Store at -20°C. Protect from light and moisture. |
| Solubility | Soluble in sterile water and bacteriostatic water for research preparation |
Compound Class & Mechanism
BI-456906-S acts as a balanced co-agonist at both the glucagon receptor (GcgR) and the GLP-1 receptor (GLP-1R). Both receptor systems couple to Gs protein-mediated cAMP-PKA signaling, with downstream effects on insulin secretion, glucagon regulation, and central appetite pathways. The dual-receptor activity profile is distinct from triple-agonist compounds (GIP/GLP-1/glucagon) and from GIP/GLP-1 dual agonists.
Research has documented pharmacodynamic effects in preclinical models associated with glucose-dependent insulinotropic activity at pancreatic beta cells, central appetite signaling through GLP-1R, and glucagon receptor-mediated hepatic fat oxidation pathway research and basal energy expenditure pathway effects. The C18 fatty-acid side chain provides DPP-IV resistance and albumin binding, extending the functional half-life suitable for weekly research administration protocols (Jungnik et al., 2023 — PMID: 36639231).
Research Findings
The survodutide-class reference compound has been investigated in preclinical and clinical research spanning metabolic pathway research, hepatic pathway research, and body composition research. Published research has documented findings in the following domains:
Key Research Areas
- Dual Receptor Co-Agonism: GcgR/GLP-1R balanced engagement pharmacology research
- Hepatic Pathway Research: GcgR-mediated hepatic fat oxidation research
- Body Composition Research: metabolic and body composition endpoints in preclinical models
- Comparative Multi-Agonist Research: dual GcgR/GLP-1R vs. triple GIP/GLP-1/Gcg co-agonist comparisons
Collectively, the survodutide-class reference compound represents a distinct research tool within the multi-receptor metabolic peptide class, offering researchers access to GLP-1 + glucagon receptor co-agonism without GIP receptor engagement (Hope et al., 2024).
Research Context
Researchers study BI-456906-S as a reference compound for dual GLP-1R/GcgR co-agonism research, particularly to investigate the distinct contribution of glucagon receptor engagement to metabolic research endpoints in the absence of GIP receptor activation. The compound’s specific dual-receptor profile distinguishes it from single-receptor and triple-receptor research peptides.
References
Zimmermann T. et al. (2022). BI 456906: discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism. PMID: 35134357
Jungnik A. et al. (2023). Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Diabetes, Obesity and Metabolism. PMID: 36639231
Le Roux CW. et al. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes & Endocrinology.
Hope DCD. et al. (2024). Glucagon-GLP-1 dual agonism: implications for body weight, glycemia, and the metabolic syndrome. Frontiers in Endocrinology.
Sanchez-Garrido MA. et al. (2017). GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia.
Henderson SJ. et al. (2016). Glucagon-like peptide-1 receptor agonism and glucagon receptor antagonism: a balanced approach for the treatment of type 2 diabetes. Obesity Reviews.
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Intended Use. This product is sold exclusively as a research chemical for use in controlled laboratory settings by qualified scientific professionals. It is intended solely for in vitro research, analytical standards, and non-clinical preclinical experimentation. The product is not a drug, dietary supplement, cosmetic, food product, or consumer article of any kind. Prohibited Uses. This product is NOT for use in humans, NOT for veterinary use, NOT for in vivo use in any species, NOT for diagnostic use, NOT for therapeutic use, NOT for food or agricultural use, and NOT for compounding into any preparation intended for administration to humans or animals. Qualified Professionals Only. Purchasers represent that they are qualified scientific professionals, licensed researchers, or authorized personnel at a research institution, and that this product will be handled in accordance with all applicable institutional, federal, state, and local regulations governing research chemicals. Regulatory Notice. The statements made regarding this product have not been evaluated by the U.S. Food and Drug Administration. This product has not been approved by the FDA for any therapeutic, diagnostic, or preventive use. Not a Compounding or Outsourcing Facility. Sirius Molecules is a research chemical supplier. Sirius Molecules is not a compounding pharmacy or outsourcing facility as defined under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. Legal Compliance. Purchasers are solely responsible for ensuring that their acquisition, possession, handling, and use of this product complies with all applicable laws and regulations in their jurisdiction. |
