Long-acting GLP-1 with Cy3 for imaging

NNC0403-0954 is a protracted GLP-1 analogue useful for imaging studies. NNC0403-0954 is a Cy3 modified version of NNC0113-0217 (also known as semaglutide). NNC0113-0217 is a GLP-1 analogue with 94% sequence homology to human GLP1 that binds and activates the GLP-1 receptor. Compared to native GLP-1, NNC0113-0217 have been designed to be long-acting in vivo. The main mechanism for the extended half-life is albumin binding. Furthermore, the NNC0113-0217 has a delayed uptake from the subcutis. Also, NNC0113-0217 is fully stable against dipeptidyl-peptidase 4 (DPP-4).

GLP-1 action is mediated via a specific interaction with GLP-1 receptors, leading to an increase in cyclic adenosine monophosphate (cAMP). GLP-1 stimulates insulin secretion in a glucose-dependent manner. Simultaneously, GLP-1 lowers inappropriately high glucagon secretion, also in a glucose­dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. Conversely, during hypoglycaemia GLP-1 diminishes insulin secretion and does not impair glucagon secretion. GLP-1 is a physiological regulator of appetite and food intake and the GLP-1 receptor is widely expressed in the brain.