Introducing Eloralintide: A Selective Amylin Receptor Agonist for Metabolic Research

Introduction to Eloralintide

Eloralintide, also known as LY3841136 or AMY-1176, is a synthetic analogue of amylin. Amylin is a 37 amino acid hormone released alongside insulin by pancreatic beta cells after nutrient intake. It participates in the regulation of food intake, satiety, gastric motility, and glucose metabolism.

Eloralintide was designed for prolonged activity and preferential activation of the human amylin 1 receptor (AMY1R). Its receptor profile and modified structure make it a subject for in vitro research into amylin signaling, peptide stability, and metabolic biology.

Chemical Structure and Properties

Eloralintide has a 37 residue main chain containing three nonstandard amino acids. It also has a modified bridge between two cysteines, an acylated lysine side chain, and a C-terminal amide. These features are part of its chemical identity and cannot be captured by an unmodified, single-letter amino acid sequence.

• CAS Number: 2883634-40-8
• FDA Unique Ingredient Identifier (UNII): 73G3354J8W
• PubChem CID: 175663130
• Molecular Formula: C₂₀₁H₃₁₉N₄₉O₆₅S₂, as represented in PubChem
• Molecular Weight: Approximately 4,526 g/mol, as computed by PubChem
• Annotated Amino Acid Sequence:
  γGlu–Cys–Asn–Thr–Ala–Thr–Cys–Ala–Thr–Gly–Orn–Leu–Ala–Glu–αMePhe–Leu–Val–Arg–Ser–Ser–Asn–NMeAsn–Phe–Gly–Pro–Lys*–Leu–Pro–Pro–Thr–Glu–Val–Gly–Ser–Asn–Thr–Tyr–NH₂

Chemical modifications:

• Nonstandard residues: Position 11 contains L-ornithine (Orn), position 15 contains alpha-methyl-L-phenylalanine (αMePhe), and position 22 contains N-methyl-L-asparagine (NMeAsn).
• N-terminal linkage: The first residue is gamma-linked L-glutamyl (γGlu).
• Modified cysteine bridge: Cysteines at positions 2 and 7 are joined by a methylene thioacetal bridge, S–CH₂–S, in place of native amylin’s disulfide bridge. This modification was designed to improve chemical stability.
• Lysine acylation: Lys* at position 26 carries a side chain containing two gamma-glutamyl units and a saturated C20 fatty diacid. This modification promotes reversible albumin binding and contributes to prolonged exposure.
• C-terminal amidation: The sequence ends in Tyr–NH₂.

Mechanism of Action

Eloralintide activates amylin receptor complexes and stimulates intracellular cyclic AMP (cAMP) signaling. Amylin receptors form when the calcitonin receptor (CTR) associates with a receptor activity modifying protein, or RAMP. CTR paired with RAMP1 forms AMY1R, while pairing with RAMP3 forms AMY3R.

In published experiments using engineered cells expressing individual human receptors, eloralintide produced the following cAMP responses:

• Human AMY1R: EC₅₀ of 23.9 pM
• Human AMY3R: EC₅₀ of 253.8 pM
• Human CTR: EC₅₀ of 291.0 pM

Under those assay conditions, eloralintide was approximately 11 times more potent at AMY1R than AMY3R and 12 times more potent at AMY1R than CTR. It showed agonist activity at all three receptors tested, with a preference for AMY1R. Separate binding assays likewise found greater affinity for human AMY1R.

Because the peptide is lipidated, albumin content can affect measured potency. Investigators observed lower apparent cellular potency when human serum albumin was added to their receptor assays. Receptor expression, species, albumin concentration, and the measured signaling endpoint should therefore be considered when interpreting results.

Findings on Food Intake and Satiety

The satiety evidence comes from several different types of measurements:

• Measured food intake in animals: Eloralintide reduced food intake in lean rats and in diet-induced obese rats. The reduction varied with the amount administered. This is direct evidence of an effect on eating behavior in those animal models.
• Reported appetite in a human study: In a 12-week phase 1 study, 14 of 73 participants receiving eloralintide (19.2%) reported decreased appetite, compared with 1 of 27 receiving placebo (3.7%). “Decreased appetite” was recorded as a reported event rather than a direct measurement of food intake.
• Direct ratings of hunger, fullness, and satiety: The same study collected exploratory appetite scores. Fasting scores showed a nonsignificant trend toward lower overall appetite with eloralintide. Post-meal scores were variable and showed no clear pattern related to amount or time. Ratings for hunger, fullness, satiety, and anticipated food consumption followed the same general pattern.

Together, these findings support further investigation of how AMY1R signaling may influence satiety and food intake. The exploratory human ratings do not yet establish the degree to which eloralintide increases the subjective feeling of fullness.

Potential Research Applications

Eloralintide offers several lines of investigation for qualified in vitro researchers:

• Amylin receptor selectivity: Compare ligand binding and cAMP responses at defined AMY1R, AMY3R, and CTR systems.
• Satiety-related signaling: Examine cellular responses in receptor models relevant to amylin’s established role in the control of food intake.
• Structure–activity relationships: Investigate how its nonstandard residues, methylene thioacetal bridge, C-terminal amidation, and fatty diacid conjugation affect chemical stability and receptor activity.
• Albumin-dependent activity: Compare receptor responses in the presence and absence of albumin.
• Species comparisons: Assess differences between human and rodent receptors. Published experiments found different relative AMY1R and AMY3R activity profiles in these systems.

Future Directions in Research

Further work may clarify which structural features contribute most to eloralintide’s receptor preference, how its signaling varies across cell types, and which biological pathways connect receptor activation with changes in food intake.

Satiety remains a specific open question. Future studies that directly measure meal size, energy intake, hunger, fullness, and post-meal satiety could help distinguish a change in eating behavior from a change in the subjective feeling of fullness. The published phase 1 appetite ratings were exploratory and did not show a clear post-meal effect.

Published results describe the studied compound and experimental material. Researchers should consult the lot-specific certificate of analysis when assessing the identity and purity of material supplied for an individual experiment.

Scientific References and Further Reading

1. Briere, D. A., et al. (2025). “Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.” Molecular Metabolism, 102, 102271. https://doi.org/10.1016/j.molmet.2025.102271
2. Bhattachar, S., et al. (2026). “Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.” Diabetes, Obesity and Metabolism, 28, 2651–2660. https://doi.org/10.1111/dom.70439
3. U.S. Food and Drug Administration. “Eloralintide — UNII 73G3354J8W.” Substance identity, synonyms, CAS mapping, and systematic structural description.
4. National Institutes of Health, PubChem. “Eloralintide — CID 175663130.” Compound representation and computed chemical properties.
5. Billings, L. K., et al. (2025). “Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2 trial.” The Lancet, 406, 2631–2643. https://doi.org/10.1016/S0140-6736(25)02155-5

Disclaimer

This product is intended for research purposes only. It is not approved for human or veterinary use, nor is it intended for clinical, diagnostic, or therapeutic applications. All research must comply with applicable local laws and institutional guidelines. Misuse of this compound for human consumption is strictly prohibited.