Cagrilintide

Research Context

Cagrilintide is a long-acting synthetic amylin analogue. It is built on a 37-residue modified human amylin / pramlintide-style backbone with three rationally designed substitutions (N14E and V17R to stabilise the central alpha-helix through a salt bridge, P37Y to enhance calcitonin-receptor potency) and N-terminal acylation with a C20 eicosanedioic fatty diacid attached via a gamma-glutamic acid linker. The fatty-diacid handle drives reversible albumin binding, extending the elimination half-life of the molecule to approximately 159 to 195 hours.

Preclinical studies have examined cagrilintide as a non-selective agonist of the amylin receptors (AMY1R, AMY2R, AMY3R) and the calcitonin receptor, with reported activity in the area postrema and hypothalamus relevant to appetite regulation and satiety signalling. The compound is the subject of ongoing late-stage investigational programmes, including combinations with semaglutide.

Chemistry & Structural Modification

Cagrilintide is a 37-amino-acid lipidated peptide. Key structural features include N14E and V17R substitutions (helix stabilisation), 25P/28P/29P proline substitutions (suppression of beta-sheet propensity and amyloid fibril formation, the primary instability mode of native human amylin), a C-terminal proline-to-tyrosine substitution (P37Y) for calcitonin-receptor activity, and N-terminal C20 fatty-diacid acylation via a gamma-Glu linker. The molecule retains the conserved Cys2-Cys7 intramolecular disulphide bridge inherited from the amylin/pramlintide scaffold.

• Molecular formula: C₁₉₄H₃₁₂N₅₄O₅₉S₂
• Molecular weight: ~4409 Da
• CAS number: 1415456-99-3; PubChem CID 171397054

Lyophilisation & Stability

Cagrilintide is supplied as a lyophilised white powder, sealed under controlled conditions. Lyophilisation removes residual moisture that would otherwise accelerate amide-bond hydrolysis and disulphide scrambling during long-term storage. The proline substitutions at positions 25, 28, and 29 were specifically engineered to suppress the beta-sheet aggregation pathway that destabilises native human amylin in aqueous solution. Sealed vials kept cold and dry retain ≥99% potency well within the labelled shelf life.

Storage

Store lyophilised vial at 2 to 8°C, protected from light. (Long-term storage at −20°C is standard practice.)

Reconstituted solution: 2 to 8°C, used within 14 to 30 days. Avoid repeated freeze–thaw cycles.

Quality & Documentation

• Purity: ≥99% by HPLC
• Certificate of Analysis (COA): published on our COA page.