Retatrutide

Description

Retatrutide Research Peptide

Retatrutide (LY3437943) is a novel triple-agonist peptide that activates the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R). As the first triple-incretin receptor agonist to enter advanced preclinical and research investigation, retatrutide represents a cutting-edge tool for studying multi-receptor metabolic signaling. This compound is supplied strictly for research use only and is not intended for human consumption.

Molecular Profile

• Molecular Weight: Approximately 4562 Da
• Classification: Triple GIP/GLP-1/glucagon receptor agonist (triagonist)
• Development Code: LY3437943
• CAS Number: 2381089-83-2
• Acylation: Contains a C-20 fatty diacid modification to facilitate albumin binding and extended pharmacokinetic duration
• Receptor Selectivity: Full agonist at GIPR; partial agonist at GLP-1R and GCGR with balanced activity ratios optimized for multi-target engagement
• Physical Appearance: White to off-white lyophilized powder

Mechanism of Action

Retatrutide engages three distinct class B G-protein coupled receptors simultaneously, each contributing complementary metabolic effects that have been characterized in preclinical research models. This triple-receptor activation profile distinguishes retatrutide from both single-agonist (GLP-1 only) and dual-agonist (GIP/GLP-1) peptides.

GLP-1 Receptor Activation: Stimulation of the GLP-1 receptor elevates intracellular cAMP in pancreatic beta cells, augmenting glucose-dependent insulin secretion. In central nervous system models, GLP-1R activation modulates hypothalamic appetite circuits, including effects on POMC-expressing neurons and melanocortin signaling pathways.

GIP Receptor Activation: GIPR engagement has been shown in preclinical research to potentiate insulin secretion in a glucose-dependent manner and to modulate adipose tissue function, including effects on lipid storage, adipokine release, and insulin sensitivity in adipocyte models.

Glucagon Receptor Activation: The glucagon receptor component provides an additional dimension absent from GLP-1 and dual-agonist peptides. Glucagon receptor activation in hepatocyte research models stimulates glycogenolysis and gluconeogenesis acutely, while chronic signaling has been associated with increased energy expenditure, enhanced hepatic lipid oxidation, and thermogenic activation in brown adipose tissue models. This glucagon component is hypothesized to drive additional energy expenditure effects observed in preclinical research with retatrutide.

The fatty acid modification enables strong binding to circulating albumin, reducing renal clearance and conferring resistance to proteolytic degradation, resulting in an extended duration of action suitable for once-weekly dosing protocols in research models.

Research Applications

• Multi-Receptor Metabolic Signaling: Comparative investigation of single-, dual-, and triple-receptor agonism on glucose homeostasis, energy balance, and lipid metabolism in preclinical models
• Energy Expenditure Research: Study of glucagon receptor-mediated thermogenesis, brown adipose tissue activation, and basal metabolic rate modulation in rodent models
• Hepatic Lipid Research: Examination of hepatic fatty acid oxidation, de novo lipogenesis, and steatosis reduction in NAFLD/NASH preclinical models
• Body Composition Analysis: Assessment of fat mass versus lean mass changes under triple-agonist administration in diet-induced obesity models
• Pancreatic Islet Biology: Evaluation of beta-cell function, proliferation, and survival under conditions of glucolipotoxicity in isolated islet and perfused pancreas models
• Receptor Cross-Talk Studies: Investigation of intracellular signaling interactions between GCGR, GIPR, and GLP-1R pathways, including effects on cAMP, beta-arrestin, and ERK1/2 signaling

Available Formulations

Retatrutide is available from Kai Bio Labs in the following lyophilized research-grade formulations:

• 2 mg — ideal for in vitro receptor binding assays and pilot cell-based studies
• 5 mg — suitable for short-duration in vivo protocols in small animal models
• 10 mg — appropriate for moderate-length preclinical research studies
• 20 mg — designed for extended in vivo studies and dose-response investigations

All vials are filled under inert nitrogen atmosphere. Reconstitute with bacteriostatic water or sterile buffer prior to experimental use.

Certificate of Analysis

• Purity: ≥98% by reverse-phase HPLC analysis
• Identity: Confirmed by LC-MS/MS and amino acid analysis
• Endotoxin Testing: LAL testing confirms endotoxin levels within research-grade acceptable limits
• Sterility: Aseptic manufacturing with sterility verification per USP methodology
• Peptide Content: Quantified by UV spectrophotometry and nitrogen analysis

A Certificate of Analysis is included with every order and available on request by lot number.

Storage and Handling

• Lyophilized Form: Store at -20°C for long-term stability; 2–8°C for short-term storage (up to 30 days)
• Reconstituted: Store at 2–8°C and use within 28 days. Avoid repeated freeze-thaw cycles
• Shelf Life: 24 months from date of manufacture at -20°C in sealed original packaging
• Light Sensitivity: Protect from direct light. Maintain in original container until ready for use
• Reconstitution: Add solvent gently along the vial wall. Swirl to dissolve — do not vortex

References

1. Coskun T, Urva S, Roell WC, et al. “LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.” Cell Metabolism. 2022;34(9):1234-1247.e9. doi:10.1016/j.cmet.2022.07.013
2. Finan B, Yang B, Ottaway N, et al. “A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.” Nature Medicine. 2015;21(1):27-36. doi:10.1038/nm.3761
3. Urva S, Coskun T, Loghin C, et al. “The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying.” Diabetes, Obesity and Metabolism. 2020;22(10):1821-1831. doi:10.1111/dom.14098
4. Day JW, Ottaway N, Patterson JT, et al. “A new glucagon and GLP-1 co-agonist eliminates obesity in rodents.” Nature Chemical Biology. 2009;5(10):749-757. doi:10.1038/nchembio.209

This product is intended for laboratory research use only. It is not a drug, food, or cosmetic and should not be used for human or veterinary diagnostic or therapeutic purposes. Handling should be performed by qualified research personnel in accordance with applicable institutional guidelines.