Eloralintide: An Amylin Receptor Agonist

Eloralintide (LY3841136) is a synthetic analog of human amylin developed by Eli Lilly and Company. Its main chain is 37 amino acids long, its native disulfide is replaced by a chemically more stable methylene thioacetal bridge, and a C20 fatty diacid on Lys26 binds albumin. In cell assays it activates the human amylin 1 receptor (AMY1R) about 12-fold more potently than the calcitonin receptor, which is what makes it a selective amylin receptor agonist. It is investigational and not approved anywhere.

This profile covers the amylin receptor family, what is published about eloralintide's structure and selectivity, what its registered trials have measured, and how the lyophilized peptide is handled in the lab. It does not cover use in people or animals. In the Anhydrolabs catalog it is listed as Eloralintide.

Eloralintide at a glance

The amylin receptor family

Amylin, or islet amyloid polypeptide, is a 37-residue hormone co-secreted with insulin by pancreatic β-cells (UniProt P10997). Its receptors are not a single gene product. They are heterodimers of the calcitonin receptor (CTR, gene CALCR, UniProt P30988) with one of three receptor activity-modifying proteins:

All are class B GPCRs that raise cyclic AMP through Gs. Because the same CTR subunit sits in every complex, selectivity between amylin receptors and the calcitonin receptor is difficult to engineer, and most amylin analogs are non-selective. Cagrilintide acts across the family, and pramlintide has been described as favoring amylin receptors over CTR only modestly. Eloralintide is the analog designed to widen that gap.

Structure

The 2025 discovery paper in Molecular Metabolism sets out the chemistry. Eloralintide is a single fatty-acid-acylated amylin analog built as a C-terminally amidated linear polypeptide of 37 amino acids in the main chain, all in the L configuration, with three non-coded residues at positions 11, 15 and 22.

Two features distinguish it from earlier amylin analogs:

• A methylene thioacetal in place of the disulfide. Native amylin, pramlintide and cagrilintide all carry a Cys2 to Cys7 disulfide. In eloralintide, those two cysteines are connected through a methylene thioacetal bond instead. The authors give chemical stability as the reason: a thioacetal bridge is not reduced or exchanged the way a disulfide is.
• A two-γ-glutamate linker to a C20 diacid at Lys26. The lysine at position 26 carries a side chain made of two γ-glutamic acid residues and a saturated, linear 20-carbon diacid. As in semaglutide, tirzepatide and cagrilintide, the diacid binds serum albumin and slows clearance.

KEGG DRUG lists the sequence as XCNTATCATGXLAEFLVRSSNNFGPKLPPTEVGSNTY, where X marks a residue KEGG cannot write in one letter. That listing places non-coded residues at positions 1 and 11, while the discovery paper places three of them at 11, 15 and 22. We have not been able to reconcile the two records, and we note the discrepancy rather than pick one. What both agree on: 37 residues, a lysine at 26, a C-terminal tyrosine, and the cysteine pair at 2 and 7.

Compared with cagrilintide

More on the older molecule is in our profile of cagrilintide.

Receptor selectivity data

In the discovery paper, UMUC3 cells expressing human AMY1R, human AMY3R or human CTR were used for binding and cAMP assays. The reported profile:

• Eloralintide activated human AMY1R about 12-fold more potently than human CTR and about 11-fold more potently than human AMY3R.
• At all three receptors it behaved as a full agonist, with maximal responses above 80% of the reference ligand.
• In rat receptors the pattern differed: both AMY1R and AMY3R were activated more potently than CTR.
• Adding 1% human serum albumin reduced the measured potency of the lipidated peptides, eloralintide and cagrilintide, while non-lipidated rat amylin and salmon calcitonin were unaffected. Selectivity for AMY1R over CTR was retained in the presence of albumin.

Two lessons for assay design follow. First, species matters: a compound's receptor balance in human cells does not carry over to rat cells. Second, albumin shifts apparent potency for any acylated analog, so the albumin content of the assay buffer has to be stated whenever potency values are reported.

Research context and trial status

Published work on eloralintide runs from cell assays through animal studies to human trials.

Animal work. The discovery paper reports studies in rats and monkeys. In rats, the authors measured food intake, body weight and body composition in a diet-induced obese model, and compared conditioned taste avoidance in lean rats against cagrilintide, a behavioral measure used to gauge aversive signaling. Pharmacokinetics were characterized in both rats and monkeys.

Human trials. Trials registered on ClinicalTrials.gov include:

The Phase 2 trial was published in the Lancet in December 2025. Its primary end point was percent change in body weight from baseline at 48 weeks, and it was completed in August 2025. As with every compound profiled here, we record what the trials measured, not how they turned out.

Trial design. Lilly's eloralintide Phase 2 study was a randomized, double-blind, placebo-controlled trial of once-weekly eloralintide alone in adults with obesity or overweight and without type 2 diabetes. The Lancet report describes the compound as a selective amylin receptor agonist in development for weight management. A second Phase 2 study (NCT07215559) tests eloralintide and macupatide, alone or in combination, against placebo in an estimated 200 adults with obesity and type 2 diabetes. The Phase 3 studies in the ENLIGHTEN program are the next stage.

Pharmacokinetics. In the Phase 1 trial, eloralintide reached maximum plasma concentration at a median of 72 to 132 hours and had a half-life of 310 to 366 hours, that is 12.9 to 15.3 days. The same paper cites 159 to 195 hours for cagrilintide. A longer half-life is a property of the molecule, not a benefit claim: for in-vitro users it mostly signals strong albumin binding.

Status. Eloralintide is investigational. It has not been approved by the FDA or any other regulator, and we found no announced marketing application at the time of writing.

Laboratory handling

Eloralintide is an acylated, ring-containing peptide of about 4.5 kDa. General practice for in-vitro stock solutions:

• Powder storage. Keep the sealed vial at −20 °C or colder, dry and protected from light. Warm it to room temperature before opening so that moisture does not condense on cold powder. See storage and handling.
• Reconstitution. A slightly basic aqueous buffer suits acylated analogs, since the diacid and the two glutamates are negatively charged above neutral pH. Add solvent down the wall of the vial and swirl gently. Our guide to reconstituting lyophilized peptides covers converting net content in mg to a concentration in mg/mL.
• The thioacetal ring. Unlike a disulfide, a methylene thioacetal is not opened by reducing agents, which removes one common route to degraded material. It does not make the peptide indestructible: the amide backbone still hydrolyzes, and the acyl chain can still be cleaved.
• Surfaces. Use low-binding tubes and tips for dilute working solutions, and include a carrier protein where the assay tolerates it, remembering that albumin also binds the lipid chain.
• Aliquots and analytics. Freeze single-use aliquots, avoid repeated freezing and thawing, and check identity and purity by mass spectrometry and reversed-phase HPLC. Shelf life in solution is shorter than in the dry state; see how long peptides last.

Anhydrolabs supplies eloralintide as a lyophilized powder in vacuum-sealed vials, and supplies its reagents in 10-vial kits as well. All material is for laboratory research only; see research use.

Where eloralintide sits in the field

Amylin analogs have become an active area alongside the incretin peptides covered in our GLP-1 receptor agonist primer and in the profile of retatrutide. The open questions for researchers are specific: how much of amylin pharmacology depends on AMY1 rather than AMY3 or CTR, whether receptor selectivity changes the signaling profile at the level of cAMP kinetics and receptor internalization, and how species differences in RAMP expression affect translation from rodent work. Eloralintide is useful as a tool compound precisely because it is the AMY1R-preferring member of a class whose other members are not selective.