GLP-3 R

Research Background

GLP-3 R (CAS 2381089-83-2) is the research designation applied to the synthetic triple-receptor agonist peptide also catalogued as retatrutide / LY3437943. It corresponds to the molecular formula C221H342N46O68 and a monomeric mass of approximately 4731 Da. Unlike single- or dual-incretin analogs, this 39-residue peptide was engineered to engage three class B G-protein-coupled receptors within receptor-expressing cell systems: the glucose-dependent insulinotropic polypeptide receptor (GIPR), the glucagon-like peptide-1 receptor (GLP-1R), and the glucagon receptor (GCGR). Because of this three-way pharmacology, laboratories frequently describe it as a triagonist scaffold. This material is supplied strictly as a reference compound for in-vitro and preclinical laboratory investigation and is not intended for human or veterinary use.

Structural Features Studied

The GLP-3 R sequence is built on a GIP-derived backbone that has been modified at several positions to alter its biochemical behavior in vitro. Structural elements characterized in the peptide-chemistry literature include:

• 2-Aminoisobutyric acid (Aib) substitutions at positions 2 and 20, non-coded residues associated with resistance to dipeptidyl peptidase-4 (DPP-4) cleavage in enzymatic-stability assays.
• An alpha-methyl-leucine residue near position 13, a modification examined in structure-activity studies of GIPR engagement.
• A C20 fatty-diacid moiety conjugated to a lysine side chain through a gamma-glutamate / AEEA linker, a feature studied for non-covalent serum-albumin association and extended in-vitro persistence.
• A C-terminal amidation, consistent with the reported formula and the ~4731 Da nominal mass.

What Has Been Studied

In published in-vitro pharmacology, this scaffold has been profiled for cyclic-AMP accumulation across cells recombinantly expressing human GIPR, GLP-1R, and GCGR, with reported half-maximal effective concentrations in the sub-nanomolar to low-nanomolar range (approximately 0.06 nM at GIPR, 0.78 nM at GLP-1R, and 5.8 nM at GCGR). This balanced-yet-differential potency profile is the primary characteristic that distinguishes it from mono- and dual-agonist reference peptides in comparative receptor panels. Reported preclinical rodent studies have employed diet-induced-obese and GLP-1R knockout mouse models together with indirect calorimetry and pair-feeding designs as experimental tools to examine how the three receptor pathways contribute to measured signaling readouts, and cell and tissue systems have been used to probe hepatic lipid handling at the biochemical level. All such work is described here only to summarize the published research literature; it remains preliminary and ongoing, and no health, therapeutic, or performance claims are made or implied.

Analytical Characterization

Each research lot of GLP-3 R is specified at greater than or equal to 99% purity. Identity and purity are established using orthogonal analytical methods common to peptide reference materials:

• Reversed-phase HPLC (typically C18, gradient elution with a water/acetonitrile mobile phase and 0.1% TFA modifier) to quantify main-peak purity and resolve related-substance and truncation impurities.
• Mass spectrometry (ESI-MS or MALDI-TOF) to confirm the observed molecular mass against the theoretical ~4731 Da value derived from C221H342N46O68, verifying identity of the intact peptide and its fatty-diacid conjugation.
• A batch-specific Certificate of Analysis (COA) documenting HPLC purity, mass-spec identity, net peptide content, and appearance for the supplied lot.

As a lyophilized peptide reference material, GLP-3 R is subject to standard laboratory handling and storage practices for research chemicals. This handling guidance pertains solely to preserving analytical integrity in the laboratory and does not imply any route of administration.