Cagrilintide (CAS 1415456-99-3) is a long-acting amylin analogue developed by Novo Nordisk (AM-833 code), composed of 37 amino acids for a molecular mass of 3904 Da. It reproduces native human amylin (IAPP, Islet Amyloid Polypeptide) structure, co-secreted with insulin by pancreatic β-cells, with three key anti-aggregation modifications (Pro25, Pro28, Pro29) inspired by pramlintide and C20 acylation (eicosanedioic acid) on Lys8 via γ-Glu/OEG linker, providing a plasma half-life of ~180 hours (≈ 7.5 days) through albumin binding.
Mechanism of action. Cagrilintide acts as an agonist of amylin receptors AMY1R, AMY2R and AMY3R, heteromeric complexes formed by the calcitonin receptor (CTR) associated respectively with RAMP1, RAMP2 and RAMP3 proteins. Activation slows gastric emptying, suppresses postprandial glucagon secretion, induces satiety via the area postrema (AP) and nucleus of the solitary tract (NTS), and reduces homeostatic and hedonic food intake.
CagriSema studies and synergy. The flagship programme combines cagrilintide + semaglutide in a single weekly injection (1:1 or 2:1 ratio). The phase Ib pilot trial (Lau 2021 Lancet) reported 17.1% weight loss over 20 weeks (vs 9.8% semaglutide alone, vs 8.1% cagrilintide alone), confirmed by phase III REDEFINE (obesity) and REIMAGINE (type 2 diabetes) trials. This synergy stems from complementary pathways: GLP-1 stimulates insulin secretion and central appetite, amylin slows absorption and suppresses glucagon.
Research use. Cagrilintide is studied preclinically for obesity, type 1 and 2 diabetes, appetite regulation and hedonic feeding behaviour (taste preference models, food-reward). DIO, ZDF and non-human primate models confirm efficacy. Lab Peptides France offers RUO cagrilintide in 5mg, 10mg and 20mg doses, with an HPLC ≥ 98% specification.
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Structure, mécanisme amyline, récepteur CTR + RAMP1/2/3, pharmacocinétique, programme REDEFINE (CagriSema), comparaison versus pramlintide Symlin, synergie GLP-1, protocoles de reconstitution RUO, stabilité et perspectives. Le pilier scientifique de référence sur le cagrilintide.
Structure, mécanisme triple agoniste, pharmacocinétique, programme TRIUMPH (1-4, Obesity, HFpEF, MASH), comparaison versus semaglutide et tirzepatide, protocoles de reconstitution RUO, stabilité et perspectives réglementaires. Le pilier scientifique de référence sur le retatrutide.