Eloralintide (LY3841136)

Verified against PubChem PUG REST, CID 175663130, properties and synonym records retrieved 17 August 2026; structural description from Briere 2025 Mol Metab full text. Fields marked “not verified” are ones we could not confirm against a primary chemical database — we leave them blank rather than guess.

Identity, and a correction to the public record

Reference material on this compound written before 2026 states that no PubChem CID exists for eloralintide, and that its CAS number, formula and molecular weight therefore rest on vendor catalogue copy alone. That is no longer accurate. A PubChem name lookup resolves eloralintide to CID 175663130, and the property record on that CID returns molecular formula C201H319N49O65S2, molecular weight 4526, and InChIKey RLBIFQNAUXZCQB-UHFFFAOYSA-N. The synonym list on the same record carries the CAS number 2883634-40-8 and the code AT53786.

The three identity values that previously circulated as vendor-only figures are therefore now confirmed against a public chemistry database, and they match. Research codes LY3841136 and LY-3841136 appear across the trial literature; the international nonproprietary name eloralintide carries the -lintide stem assigned to amylin mimetics.

One identity field remains genuinely unavailable. The full amino-acid sequence has not been published. Briere 2025 describes the architecture in prose but does not disclose the residue-by-residue sequence, and no database record supplies it. That field is recorded here as unknown rather than inferred.

Receptor selectivity, in numbers

Amylin receptors are heterodimers: the calcitonin receptor paired with one of three receptor activity-modifying proteins, giving the AMY1R, AMY2R and AMY3R subtypes. Selectivity across those subtypes is the design premise of this molecule, and Briere and colleagues 2025 measured it in cAMP accumulation assays in cell lines expressing each receptor individually.

At the human receptors, the reported EC50 was 23.9 pM (SE 1.1) at AMY1R, 291.0 pM (SE 27.0) at the calcitonin receptor, and 253.8 pM (SE 9.7) at AMY3R. Those correspond to roughly 12-fold and 11-fold potency differences favouring AMY1R. Full agonism was reported at all three human receptors, with maximal effect above 80 percent.

At the rat receptors the pattern differed. Reported EC50 values were 5.4 pM (SE 0.5) at rat AMY1R, 243.2 pM (SE 27.5) at rat calcitonin receptor and 13.8 pM (SE 0.9) at rat AMY3R, giving roughly 45-fold separation from the calcitonin receptor but only about 3-fold from AMY3R. The species difference is substantial and is worth carrying into any reading of the rodent data.

Molecular design

Briere 2025 describes the construct directly. The main polypeptide chain contains 37 amino acids, including three non-coded residues at positions 11, 15 and 22. The disulfide bridge present in native amylin is replaced with a methylene thioacetal bridge, which the authors state enhances chemical stability. The main chain is conjugated to a C20 fatty diacid moiety through a linker at the lysine residue at position 26.

The stated purpose of the acylation is albumin binding, used as a half-life extension mechanism to support once-weekly administration. Native amylin aggregates and has a short circulating life; the substitutions address both properties.

Whether the design achieved its half-life objective is measurable rather than asserted. In the Phase 1 single-ascending-dose study, plasma concentrations declined monophasically after peak, and the terminal geometric mean half-life was 310 to 366 hours, or 12.9 to 15.3 days, across the 0.4 mg to 12 mg range. The authors noted that half-life could not be calculated reliably at the two lowest doses studied.

Rodent findings, including the aversion comparison

Pharmacokinetics were characterised in male Sprague-Dawley rats and cynomolgus monkeys by liquid chromatography-tandem mass spectrometry. Pharmacodynamic work used two rat populations: lean Sprague-Dawley rats and diet-induced obese Long Evans rats.

In the diet-induced obese rats, Briere 2025 reported dose-dependent reductions in food intake and body weight, with the weight change described as primarily fat-mass loss.

The comparison that distinguishes this molecule from its class is the aversion measurement. Conditioned taste avoidance was assessed in lean rats given free access to a 0.15 percent saccharin solution. The authors reported that eloralintide induced significantly less conditioned taste avoidance than cagrilintide, a non-selective amylin receptor agonist, at p below 0.05. That is the specific preclinical observation the selective-versus-non-selective design argument rests on, and it is a single comparison in one species. It has not been replicated by an independent group in the retrieved literature.

The published human record

Three human studies have been reported in peer-reviewed journals. In the Phase 1 single-ascending-dose study, NCT05295940, 48 healthy participants with mean BMI 27.5 received single subcutaneous doses from 0.04 to 12 mg. At week 4, mean percent change from baseline in body weight was -2.5 percent at 4 mg (p<0.01) and -4.4 percent at 12 mg (p<0.001), against +0.6 percent for placebo. Nine participants in eloralintide cohorts reported 16 adverse events, 15 of them mild.

A 12-week Phase 1 multiple-ascending-dose study randomised 100 participants at three United States centres, mean age 44, mean BMI 32.6. At week 12 the least-squares mean percent reduction in body weight across dose groups ranged from 2.6 to 11.3 percent. Reported treatment-emergent adverse events included decreased appetite in 19 percent, headache 12 percent, fatigue 11 percent, diarrhoea 10 percent, nausea 8 percent and vomiting 4 percent.

The Phase 2 trial, NCT06230523, randomised 263 participants across 46 United States centres for 48 weeks. Mean percent change in body weight ranged from -9 percent at 1 mg to -20 percent at 9 mg, against -0.4 percent for placebo.

What is not known

The AMY2R subtype has not been characterised. Briere 2025 names AMY2R in its description of receptor biology but reports potency at AMY1R, AMY3R and the calcitonin receptor only, so the selectivity profile is incomplete by one of four relevant targets. The full amino-acid sequence remains undisclosed, which prevents independent structural verification. The single-species aversion comparison against cagrilintide has not been replicated by an independent group. Human exposure to date is bounded: the longest published trial ran 48 weeks in 263 participants, and the Phase 2 population was 78 percent female and 78 percent White, recruited entirely in the United States, and excluded people with type 2 diabetes. No published trial has reported outcomes beyond 48 weeks, and no cardiovascular outcome data exist. Special populations are under active study rather than reported: registered Phase 1 protocols in hepatic impairment, severe renal impairment and end-stage renal disease are recruiting, with primary completion dates in 2026 and 2027. Weight regain after discontinuation, effects on lean versus fat mass in humans, bone density, and interactions with incretin agents outside the ongoing combination studies are all unmeasured in the published record.

Questions