Key findings
- The development report identifies amylin's high propensity toward amyloid fibril formation as the design constraint, and describes the structure-activity work that selected this stable lipidated analogue from the series. [1]
- Across 25 receptor endpoints the analogue behaved as a nonselective agonist of calcitonin family G protein-coupled receptors, with a profile of binding, activation and regulation distinct from six selective and nonselective comparator agonists. [2]
- In mice lacking receptor activity-modifying proteins 1 and 3 the body weight response was impeded and the area postrema c-Fos signal fell by 57 percent relative to wild-type, which the authors read as a dependence on amylin receptors 1 and 3. [3]
- Single-nucleus RNA sequencing across rat, mouse and non-human primate caudal brainstem found long-term transcriptional changes in nucleus of the solitary tract Calcr and Prlh cells in rats but not in mice. [4]
Identity and structure
- Receptor profile
- A nonselective agonist of calcitonin family G protein-coupled receptors, acting at the calcitonin receptor and at amylin receptors formed as heterodimers of that receptor with receptor activity-modifying proteins [2][3]
- Development code
- Described in the receptor pharmacology report as AM833 [2]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The chemistry report frames the molecule as a stability problem first. Amylin readily forms amyloid fibrils and the shorter-acting analogue pramlintide has a short half-life, so the structure-activity work aimed at a lipidated analogue that is stable and long-acting, and selected the analogue numbered 23 in that series. [1]
The receptor pharmacology report resolves the profile rather than a single potency. Comparing the analogue with amylin-selective and nonselective lipidated analogues, with pramlintide and with salmon calcitonin across binding, activation and regulation endpoints, the authors conclude that it occupies a pharmacological profile none of the comparators share. [2][5]
Knockout work localizes the weight response to specific receptor subtypes and brain regions: without receptor activity-modifying proteins 1 and 3 the weight response was impeded and the area postrema c-Fos signal was reduced, while the cross-species sequencing work points to nucleus of the solitary tract Calcr and Prlh cells as the population whose sustained transcriptional response differs between rats and mice. [3][4]
Research findings
In vitro
- System
- A series of lipidated amylin analogues explored in medicinal chemistry, with amylin's propensity to form amyloid fibrils named as the design challenge
- Measured
- Structure-activity relationships across the analogue series
- Reported
- The stable lipidated long-acting analogue numbered 23 in the series was selected from the structure-activity work. [1]
In vitro
- System
- Calcitonin receptor and amylin receptor assays, compared with two lipidated analogues, pramlintide, salmon calcitonin, human calcitonin and rat amylin
- Measured
- Twenty-five endpoints covering receptor binding, receptor activation and receptor regulation
- Reported
- The analogue showed a pharmacological profile across these endpoints that differed from every comparator, acting at both amylin receptors and the calcitonin receptor. [2]
In vitro
- System
- Receptor-specific potency assays comparing this analogue with the salmon calcitonin derived agonist KBP-336
- Measured
- Potency at the amylin receptor and at the calcitonin receptor
- Reported
- Both peptides activated the amylin and the calcitonin receptor, with KBP-336 more potent and biased toward the calcitonin receptor. [5]
Preclinical in vivo
- System
- High-fat-diet obese rats and Zucker diabetic fatty rats, head to head with KBP-336
- Measured
- Body weight, fasting blood glucose, HbA1c and insulin action
- Reported
- Both peptides lowered body weight in the high-fat-diet rats, with the highest amount of KBP-336 exceeding this analogue; in the diabetic rats both improved the glucose measures, with KBP-336 superior for glucose control. [5]
Preclinical in vivo
- System
- Wild-type mice and littermates lacking receptor activity-modifying proteins 1 and 3, fed a high-fat diet, with salmon calcitonin as comparator
- Measured
- Body weight, food intake, c-Fos activity in the dorsal vagal complex and lateral parabrachial nucleus, and differential gene expression in those regions and the mediobasal hypothalamus
- Reported
- Body weight fell in wild-type mice and food intake fell over the first days; the knockout impeded the analogue's potency, and the area postrema c-Fos signal was 57 percent lower than in wild-type, while neither peptide significantly altered gene expression in the two regions after three weeks. [3]
Preclinical in vivo
- System
- Rat, mouse and non-human primate caudal brainstem, profiled by single-nucleus RNA sequencing with spatial profiling in the rat; reported as a preprint
- Measured
- Cell population structure across 89 populations, neuron distribution, and acute and long-term transcriptional responses
- Reported
- Long-term transcriptional changes including raised prolactin releasing hormone expression appeared in rat nucleus of the solitary tract Calcr and Prlh cells but not in mouse; activating rat area postrema Calcr cells briefly reduced food intake but did not sustain the reduction. [4]
Handling for in-vitro work
- Aggregation state in the cited work
- The development report names amylin's propensity toward amyloid fibril formation as the constraint the lipidated analogue was designed against, so aggregation state belongs in the method record for this material [1]
- Comparators in the cited work
- The receptor and rodent reports run this analogue against pramlintide, salmon calcitonin or a calcitonin-derived agonist in the same experiment, so a comparator peptide is part of the method record [2][5]
- Storage
- Lyophilized at −20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- The cross-species sequencing source is a preprint rather than a peer-reviewed report, and the rat and mouse results it describes diverge, so the species dependence it reports is not settled in the cited work.
- The cited work does not establish which receptor subtype accounts for the calcitonin receptor component of the profile in the rodent models, since the knockout study removed two receptor activity-modifying proteins together.
- None of the cited work reports an analytical identity check that would distinguish this lipidated analogue from another amylin or calcitonin analogue in a supplied lot.
Clinical literature on this analogue exists, including work on a combination with a GLP-1 analogue, and concerns finished formulations; it is out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
No published lot is available for this exact compound name.
Read a certificate of analysis ↗References
- Kruse T, Hansen JL, Dahl K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of medicinal chemistry. 2021.
- Fletcher MM, Keov P, Truong TT, et al. AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. The Journal of pharmacology and experimental therapeutics. 2021.
- Carvas AO, Leuthardt A, Kulka P, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025.
- Ludwig MQ, Coester B, Gordian D, et al. A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance. bioRxiv : the preprint server for biology. 2025.
- Larsen AT, Mohamed KE, Sonne N, et al. Does receptor balance matter? - Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.