Retatrutide Molecular Profile: Formula, Weight, CAS Number, Sequence and Structure

Retatrutide (developer code LY3437943) is an investigational synthetic peptide developed by Eli Lilly and Company. Structurally it is a lipidated (fatty-diacid-acylated) peptide, and pharmacologically it acts as a balanced triple agonist of three receptors: the GLP-1 receptor (GLP-1R), the GIP receptor (GIPR) and the glucagon receptor (GCGR). It was first described by Coskun et al. in Cell Metabolism (2022) and evaluated in a Phase 2 obesity study reported by Jastreboff et al. in the NEJM (2023).

Investigational status: As of May 2026, retatrutide is investigational and has not been approved by the TGA, FDA, EMA or any other regulator. This page is a molecular and scientific reference intended for Australian researchers; it is provided for research use only and is not medical advice or a treatment recommendation.

This page focuses on the molecule itself: its formula, mass, registry identifiers, amino-acid sequence and the structural chemistry that governs its behaviour. For experimental context and study design, see the Retatrutide research guide and the aggregated trial data in Retatrutide statistics 2026.

Retatrutide is a single-chain peptide of 39 amino acids. Its one-letter backbone sequence is:

YAQGTFTSDYSILLDKKAQAAFIEYLLEGGPSSGAPPPS (39 residues)

The peptide carries several deliberate chemical modifications that distinguish it from the native incretin and glucagon backbones and confer its stability and receptor profile:

• 2-aminoisobutyric acid (Aib) substituted at positions 2 and 20, which resist enzymatic cleavage and stabilise the helical structure.
• alpha-methyl-L-leucine at position 13, a further non-natural residue.
• C-terminal amidation (the terminal residue is a serinamide rather than a free acid).
• One lysine side chain acylated with a C20 fatty diacid (eicosanedioic acid), attached through a gamma-glutamate plus AEEA-type linker. This lipid moiety enables non-covalent albumin binding, the key feature that extends the molecule's half-life.

The fatty acid is a C20 diacid; the linker is described here generically because the exact spacer count is not firmly established in the public record. Because the backbone, the non-natural residues and the acyl chain together determine how retatrutide engages each receptor, the sequence and these modifications underpin everything discussed in the mechanism section below.

The table below lists the confirmed physicochemical and identifier data for retatrutide. Every value is drawn from public chemistry registries; entries are deliberately conservative, with no exact/monoisotopic mass and no asserted solubility or storage specifications.

For laboratory handling and reconstitution considerations, refer to the peptide reconstitution and storage guide rather than treating any single figure as an authoritative specification. Registry records can be cross-checked on PubChem and CAS Common Chemistry.

Retatrutide's standout pharmacokinetic feature is a long plasma half-life of approximately six days, which is what allows the investigational once-weekly subcutaneous dosing interval (the Phase 2 study used titrated dosing up to 12 mg/week). This durability is engineered into the molecule rather than incidental.

The mechanism is the acylation described earlier. A lysine side chain carries a C20 fatty diacid (eicosanedioic acid) connected through a gamma-glutamate and AEEA-type linker. This lipid tail binds non-covalently to serum albumin, the most abundant plasma protein. Because albumin circulates with a long lifetime and is too large to be filtered readily by the kidney, the bound peptide is effectively shielded from rapid renal clearance and enzymatic degradation. The peptide stays associated with albumin in a dynamic equilibrium, releasing slowly to engage its receptors.

The combination of the Aib substitutions (which resist peptidase cleavage) and albumin-anchoring acylation is what converts a peptide that would otherwise clear within hours into one with a multi-day half-life.

For how this pharmacokinetic profile maps onto experimental dosing schedules, see the retatrutide dosing protocol reference. Note that no precise terminal half-life value is asserted here; "approximately six days" is the appropriate level of precision for a molecule still under investigation.

Retatrutide is a balanced triple agonist, meaning a single molecule activates three distinct class B G-protein-coupled receptors. The 39-residue backbone is engineered so that overlapping pharmacophores can each dock into a different receptor, producing a combined incretin-and-glucagon signal that no native hormone delivers alone.

• GLP-1 receptor (GLP-1R) — incretin signalling that drives glucose-dependent insulin secretion and satiety. See GLP-1 explained.
• GIP receptor (GIPR) — the second incretin axis, contributing to insulin secretion and metabolic signalling. See GIP receptor explained.
• Glucagon receptor (GCGR) — agonism here is associated with increased energy expenditure. See glucagon receptor explained.

In broad terms, the GLP-1 and GIP incretin actions support insulin secretion and satiety signalling, while the glucagon-receptor component adds an energy-expenditure dimension. The non-natural residues (Aib at 2 and 20, alpha-methyl-L-leucine at 13) and the C-terminal amide help tune both receptor engagement and stability, so that the same molecule can hold a balanced affinity across all three targets. Receptor and ligand annotations for retatrutide are catalogued in the IUPHAR/BPS Guide to Pharmacology and ChEMBL.

Sources:

• PubChem CID 171390338
• CAS Common Chemistry — 2381089-83-2
• ChEMBL CHEMBL5095485
• IUPHAR/BPS Guide to Pharmacology
• Coskun et al., Cell Metabolism (2022)
• Jastreboff et al., NEJM (2023)