Overview
GLP-3R is a research-grade reference compound within the emerging triple-agonist peptide class, engineered for balanced activity at three metabolic receptor systems: the GIP receptor, the GLP-1 receptor, and the glucagon receptor (GcgR). Investigated in preclinical and clinical research, the compound represents the most complex receptor-engagement profile yet developed in the metabolic peptide class (Coskun et al., 2022 — PMID: 37385105).
History
The triple-agonist peptide class emerged from research efforts to simultaneously engage three metabolic receptor systems within a single molecule, investigating whether the addition of glucagon receptor agonism to dual incretin activity could produce complementary pharmacodynamic effects in preclinical models. Research has characterized the class’s unique triple-receptor engagement profile, with particular focus on the role of hepatic fat oxidation and basal energy expenditure pathways mediated through GcgR (Jastreboff et al., 2023).
Structure & Molecular Data
| CAS Number | 2381089-83-2 |
| Molecular Formula | C₂₂₁H₃₄₃N₄₉O₆₅ |
| Molecular Weight | 4,731.41 g/mol |
| Amino Acid Count / Structure | 39-amino-acid triple agonist peptide |
| PubChem CID | 162641593 |
| Sequence | 39-residue synthetic triple agonist peptide engineered for balanced activity across GIP, GLP-1, and glucagon receptors with extended half-life modifications |
| Appearance | Lyophilized white powder |
| Storage | Store at -20°C. Protect from light and moisture. |
| Solubility | Soluble in sterile water and bacteriostatic water |
Compound Class & Mechanism
GLP-3R acts as a balanced agonist at three receptors: GIP receptor, GLP-1 receptor, and glucagon receptor (GcgR). Each receptor couples to Gs protein-mediated cAMP-PKA signaling but with distinct tissue distribution profiles. Research has characterized GcgR engagement as contributing hepatic fat oxidation pathway research endpoints and basal energy expenditure research effects not accessible through GIP/GLP-1 receptor activation alone.
The molecule’s triple-receptor activity profile represents the broadest metabolic receptor coverage of any compound in the class. Research has documented pharmacodynamic effects in preclinical models associated with glucose-dependent insulinotropic activity, central appetite modulation, and glucagon receptor-mediated hepatic and thermogenic pathways. Structural modifications provide DPP-IV resistance and extended half-life suitable for weekly research administration protocols (Jastreboff et al., 2023 — PMID: 37366315).
Research Findings
The GLP-3R-class reference compound has been investigated in preclinical and Phase 2 clinical research spanning metabolic pathway research, hepatic pathway research, and energy expenditure pathway studies. Published research has documented findings in the following domains:
Key Research Areas
- Triple Receptor Co-Agonism: GIPR/GLP-1R/GcgR balanced engagement pharmacology
- Hepatic Pathway Research: GcgR-mediated hepatic fat oxidation research
- Energy Expenditure Research: basal metabolic rate and thermogenic pathway research
- Body Composition Research: preclinical research into body composition endpoints
Collectively, the GLP-3R-class reference compound represents the current frontier of multi-receptor incretin-class peptide research, offering researchers a tool for investigating the complete span of metabolic receptor pharmacology accessible through synthetic peptide engineering (Coskun et al., 2022).
Research Context
Researchers study GLP-3R as a reference compound for triple-receptor agonist pharmacology, particularly to investigate the distinct contribution of glucagon receptor engagement to metabolic research endpoints. The compound’s triple-receptor engagement profile makes it uniquely positioned for investigating combined hepatic, thermogenic, and classical incretin pathway research.
References
Coskun T. et al. (2022). LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist. Cell Metabolism. PMID: 37385105
Jastreboff AM. et al. (2023). Triple-hormone-receptor agonist [GLP-3R] for obesity — a phase 2 trial. NEJM. PMID: 37366315
Rosenstock J. et al. (2023). [GLP-3R], a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. Lancet.
Urva S. et al. (2023). LY3437943, a novel triple GIP/GLP-1/glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet.
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.
Regulatory & Legal Notice
| REGULATORY & LEGAL NOTICE
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. |
