Novo Nordisk, Novo Nordisk Park, DK-2760 Maaloev, Denmark.
J Med Chem. 2021 Aug 12;64(15):11183-11194. doi: 10.1021/acs.jmedchem.1c00565. Epub 2021 Jul 21.
A hallmark of the pancreatic hormone amylin is its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug design effort. The amylin analogue pramlintide is commercially available for diabetes treatment as an adjunct to insulin therapy but requires three daily injections due to its short half-life. We report here the development of the stable, lipidated long-acting amylin analogue cagrilintide () and some of the structure-activity efforts that led to the selection of this analogue for clinical development with obesity as an indication. Cagrilintide is currently in clinical trial and has induced significant weight loss when dosed alone or in combination with the GLP-1 analogue semaglutide.
胰岛激素胰淀素的一个显著特点是其具有很高的形成淀粉样纤维的倾向，这使得它成为一项具有挑战性的药物设计工作。胰淀素类似物普兰林肽可作为胰岛素治疗的辅助药物，用于治疗糖尿病，但由于其半衰期短，需要每日注射三次。我们在此报告了稳定的、脂化的长效胰淀素类似物 cagrilintide（）的开发，以及一些导致选择该类似物用于肥胖适应症的临床开发的结构活性研究。Cagrilintide 目前正在进行临床试验，单独或与 GLP-1 类似物 semaglutide 联合使用时，可显著减轻体重。
