posted on 2021-07-21, 17:36authored byThomas Kruse, Jakob Lerche Hansen, Kirsten Dahl, Lauge Schäffer, Ulrich Sensfuss, Christian Poulsen, Morten Schlein, Ann Maria Kruse Hansen, Claus Bekker Jeppesen, Charlotta Dornonville de la Cour, Trine Ryberg Clausen, Eva Johansson, Simone Fulle, Rikke Bjerring Skyggebjerg, Kirsten Raun
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.