Retatrutide (LY3437943), 99.9% Purity Peptide 20mg Not For Human Use, Lab Use Only.
Sequence: Tyr-{Aib}-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{α-Me-Leu}-Leu-Asp-Lys-{diacid-C20-gamma-Glu-(AEEA)-Lys}-Ala-Gln-{Aib}-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 (Sodium salt)
Amino acid length: 39
Purity: 99.9%
Method: HPLC
Molecular formula: C221H342N46O68
Molecular weight: 4731.33
CAS#: 2381089-83-2
Source: Synthetic
Form: Powder
Description: Retatrutide is the first triple agonist peptide targeting the Glucagon, GLP-1, and GIP receptors (3G), the EC50 values are 5.79 nM, 0.0643 nM, and 0.775 nM respectively [1].
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].
Storage: This peptide will normally be delivered in lyophilized form and stored in a freezer at or below -20 °C. For more details, please refer to the manual:
Reference:
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, 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
About TFA Salt: Trifluoroacetic acid (TFA) significantly impacts 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.
When present in custom peptides, TFA residues 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 trifluoroacetate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.