Retatrutide (LY3437943), 99.70% purity peptide (TFA removed)

• COA/MS/HPLC Report
• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

Among its predecessors, Liraglutide (Victoza, Saxenda), Exenatide (Byetta), Semaglutide (Ozempic, Rybelsus, Wegovy), Lixisenatide (Adlyxin), Dulaglutide ( Trulicity) are GLP-1 receptor agonists, Tirzepatide (Mounjaro) is a GLP-1/GIP dual receptor co-agonist. Survodutide is a Glucagon/GLP-1 dual receptor co-agonist.

Retatrutidere is administered subcutaneously, with a half-life of 6 days, and therefore can be injected weekly [2]. After 48 weeks, Retatrutide achieved 24.2% weight loss in obese or overweight patients and produced 17% weight loss in diabetic patients, making it arguably the most powerful pipeline today. In addition, Retatrutide also achieved up to 86% reduction in liver fat in patients with NASH (non-alcoholic steatohepatitis) [2].

A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The liver fat (LF) reduction at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo)[3].

• 1. Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z. 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 Metab. 2022 Sep 6;34(9):1234-1247.e9.
• 2. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial [published online ahead of print, 2023 Jun 26]. N Engl J Med. 2023;10.1056/NEJMoa2301972.
• 3. Sanyal, Arun J et al. “Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.” Nature medicine vol. 30,7 (2024): 2037-2048. doi:10.1038/s41591-024-03018-2
• 4. Ma, Jun et al. “Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice.” Endocrine, 10.1007/s12020-024-03998-8. 30 Aug. 2024, doi:10.1007/s12020-024-03998-8

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.