Retatrutide (LY-3437943) is an experimental drug developed by Eli Lilly for the treatment of obesity. It is a triple agonist targeting the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R).
In a phase 2 trial, retatrutide demonstrated a mean weight reduction of over 17.5% in adults with obesity or preobesity without diabetes. The drug is a peptide with a specific amino acid sequence and unique chemical modifications, including 2-aminoisobutyric acid, alpha-methyl leucine, and a modified lysine tail.
Retatrutide has shown efficacy in improving glucose tolerance and causing significant body weight loss through glucagon receptor activation. It is currently being investigated in phase 3 clinical trials, with results indicating its potential to outperform existing obesity treatments in terms of total weight loss.
The drug’s safety profile is similar to other GLP-1 and GIP-GLP-1 receptor agonists, with mostly mild to moderate gastrointestinal adverse events reported during dose escalation. Retatrutide’s ability to achieve substantial weight reduction and improve cardiometabolic measures makes it a promising candidate for obesity treatment.
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| Other Names | EX-A7826E |
|---|---|
| IUPAC Name | 20-[[(1S)-4-[2-[2-[2-[[(5S)-5-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S, 3R)-2-[[(2S)-2-[[(2S, 3R)-2-[[2-[[(2S)-5-amino-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-methylpropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-2, 4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]hexanoyl]amino]-6-[[(2S)-1-[[(2S)-5-amino-1-[[1-[[(2S)-1-[[(2S)-1-[[(3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1, 5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid |
| CAS | 2381089-83-2 |
| Molecular Weight | 4731 |
| Molecular Formula | C221H342N46O68 |
| SMILES | CC[C@H](C)C(C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N4CCC[C@H]4C(=O)N5CCC[C@H]5C(=O)N[C@@H](CO)C(=O)N)NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)[C@H](C)NC(=O)C(C)(C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@](C)(CC(C)C)NC(=O)C([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CC7=CC=C(C=C7)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC8=CC=CC=C8)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)C(C)(C)NC(=O)[C@H](CC9=CC=C(C=C9)O)N |