Description

Overview

Retatrutide is a synthetic 39-amino-acid engineered peptide designed to bind and activate three distinct metabolic hormone receptors: GLP-1R, GIPR, and GCGR. By integrating glucagon receptor agonism alongside incretin targets, Retatrutide offers a multi-pathway mechanism distinct from dual-agonist peptides.

The structure incorporates an α-aminoisobutyric acid (Aib) substitution for DPP-IV resistance and a specialized C₂₀ fatty-diacid acyl chain attached to a Lysine residue. This lipidation promotes reversible conjugation to circulating serum albumin, yielding an extended half-life of approximately 6 days in vivo.

Key Technical Specifications

Sequence	`HXQGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS-NH2` (X = Aib; Lys conjugated to γGlu-C20 diacid; C-terminal amide)
Molecular Formula	C₂₂₁H₃₄₂N₄₆O₆₈
Molecular Weight	~4731.3 g/mol
CAS Number	2381089-83-2
Elimination Half-Life	~6 days (in vivo, human)
Solubility	Bacteriostatic Water / Sterile Water
Primary Class	Multi-Receptor Incretin / Glucagon Agonist

Biochemical Architecture & Mechanisms

1. Balanced Triple-Receptor Potency

Retatrutide exhibits targeted activation across three distinct G-protein coupled receptors (GPCRs):

GIP Receptor Agonism: High relative potency at GIPR drives potent glucose-dependent insulinotropic signaling.
GLP-1 Receptor Agonism: Engages GLP-1R pathways involved in satiety modulation and postprandial signaling.
Glucagon Receptor Agonism: Direct activation of GCGR contributes to increased energy expenditure, thermogenesis, and modified hepatic lipid handling.

2. Structural Stabilization & Albumin Conjugation

The introduction of non-canonical Aib residues protects the peptide backbone against enzymatic cleavage by Dipeptidyl Peptidase IV (DPP-IV). The C₂₀ diacid side chain binds tightly but reversibly to human serum albumin, creating a depot effect that minimizes renal clearance.

Nomenclature Clarification: Marketing literature occasionally references Retatrutide as “GLP-3.” However, no native GLP-3 receptor exists in human biology; the terminology refers to its triple action across GLP-1, GIP, and Glucagon receptors.

For laboratory research, educational, and analytical reference only. Strictly not for human or veterinary use.