Development of Cagrilintide, a Long-Acting Amylin Analogue,Journal of Medicinal Chemistry

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Development of Cagrilintide, a Long-Acting Amylin Analogue
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-07-21 , DOI: 10.1021/acs.jmedchem.1c00565
Thomas Kruse ₁ , Jakob Lerche Hansen ₁ , Kirsten Dahl ₁ , Lauge Schäffer ₁ , Ulrich Sensfuss ₁ , Christian Poulsen ₁ , Morten Schlein ₁ , Ann Maria Kruse Hansen ₁ , Claus Bekker Jeppesen ₁ , Charlotta Dornonville de la Cour ₁ , Trine Ryberg Clausen ₁ , Eva Johansson ₁ , Simone Fulle ₁ , Rikke Bjerring Skyggebjerg ₁ , Kirsten Raun ₁

Affiliation

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 (23) 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.

中文翻译：

长效胰淀素类似物卡格林肽的开发

胰腺激素胰淀素的一个标志是其高度倾向于形成淀粉样蛋白原纤维，这使其成为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手段用于糖尿病治疗，但由于其半衰期短，需要每天注射 3 次。我们在此报告了稳定的脂化长效胰淀素类似物卡格林肽 ( 23 ) 的开发以及一些结构-活性研究，这些努力导致选择这种类似物用于以肥胖为适应症的临床开发。Cagrilintide 目前正在进行临床试验，当单独给药或与 GLP-1 类似物 semaglutide 联合给药时，可引起显着的体重减轻。

更新日期：2021-08-12

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