Retatrutide

Retatrutide (LY-3437943) is an experimental drug for obesity developed by American pharmaceutical company Eli Lilly and Company. It is a triple glucagon hormone receptor agonist (GLP-1, GIP, and GCGR receptors).^[1] It has been shown to achieve a more than 17.5% mean weight reduction in adults without diabetes but with obesity or preobesity (overweight) during a phase 2 trial.^[2][3][4]

Retatrutide

Clinical data
Other names	LY-3437943
Identifiers
IUPAC name L-tyrosyl-2-methylalanyl-L-glutaminylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-alpha -aspartyl-L-tyrosyl-L-seryl-L-isoleucyl-2-methyl-L-leucyl-Lleucyl-L-alpha -aspartyl-L-lysyl-N6-(N-(19-carboxy-1-oxononadecyl)-L-gamma-glutamyl-2-(2-(2-aminoethoxy)ethoxy)acetyl)-L-lysyl-L-alanyl-L-glutaminyl-2-methylalanyl-L-alanyl-Lphenylalanyl-L-isoleucyl-L-alpha -glutamyl-L-tyrosyl-L-leucyl-L-leucyl-L-alpha -glutamylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-prolyl-L-serinamide
CAS Number	2381089-83-2
UNII	NOP2Y096GV
ChEMBL	ChEMBL5095485
Chemical and physical data
Formula	C223H343F3N46O70
Molar mass	4845.444 g·mol−1

Chemistry

The drug is a peptide with amino acid sequence^[5]

YA¹QGTFTSDYSIL²LDKK⁴AQA¹AFIEYLLEGGPSSGAPPPS³

where superscript numbers refer to unique chemical modifications:

1. "A¹" refers to 2-aminoisobutyric acid (AiB) instead of alanine.
2. "L²" refers to alpha-methyl added to leucine (MeL, 2-methylleucine).
3. "S³" refers to addition of an amino group to the C-terminal serine.
4. "K⁴" refers to a modification group attached to the lysine's tail amine, specifically (AEEA)-gamma-Glu-C20 diacid.

References

1. Coskun T, Urva S, Roell WC, et al. (September 2022). "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. 34 (9): 1234–1247.e9. doi:10.1016/j.cmet.2022.07.013. PMID 35985340. S2CID 251675508.
2. "Lilly's phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight". investor.lilly.com (Press release). Eli Lilly. 26 June 2023. Retrieved 3 July 2023.
3. Constantino, Annika Kim (26 June 2023). "Eli Lilly experimental obesity drug could beat rivals in total weight loss for patients". CNBC.com. Retrieved 3 July 2023.
4. Jastreboff AM, Kaplan LM, Frías JP, et al. (June 2023). "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial". The New England Journal of Medicine. 389 (6): 514–526. doi:10.1056/NEJMoa2301972. PMID 37366315. S2CID 259260926. Free access subject to registration.
5. "Compound Report Card". ebi.ac.uk. European Bioinformatics Institute, European Molecular Biology Laboratory. n.d. Retrieved August 5, 2024.