GMP PCL Cagrilintide 10mg

Cagrilintide is a synthetic, long-acting amylin analogue engineered to improve peptide stability and extend half-life relative to native amylin. It incorporates key modifications, including 14E/17R mutations to stabilize an α-helical segment via a salt bridge, multiple proline substitutions (25P, 28P, 29P) to reduce β-sheet formation, and N-terminal C20 fatty diacid lipidation for reversible albumin binding (Kruse et al. 2021). These design features yield a pharmacokinetic profile suitable for once-weekly administration, with a reported elimination half life of 7–8 days (D’Ascanio et al. 2024).

Functionally, cagrilintide activates amylin receptors AMY1R, AMY2R, AMY3R and the calcitonin receptor (CTR), binding via a conserved “bypass” motif involving mid-segment residues (S19– P25) (Cao et al. 2025). Structural analyses show that cagrilintide mimics amylin’s receptor engagement while introducing conformational differences at select positions, such as Pro37, which enhances CTR interaction and modulates receptor dynamics (Cao et al. 2025). These receptor-specific dynamics suggest altered signaling profiles compared to other amylin-based peptides.

In vitro and preclinical studies indicate that cagrilintide retains high potency across amylin and calcitonin receptor subtypes and demonstrates additive pharmacodynamic effects when combined with GLP-1 agonists like semaglutide (D’Ascanio et al. 2024). Its dual-receptor agonism and extended activity profile position it as a promising candidate for further investigation in weight regulation models. Importantly, formulation efforts emphasize stability under physiological conditions and resistance to fibril formation—a limitation of earlier analogues such as pramlintide (Kruse et al. 2021).