Liver-preferential insulin analogue

Insulin is a peptide hormone acting as a key regulator of glucose homeostasis. Insulin binds to the insulin receptor (InsR), which exists in two alternatively spliced isoforms, InsR-A and InsR-B. The insulin receptor belongs to the same family of receptor tyrosine kinases as the IGF1 receptor (IGF1R) and insulin is therefore also able to bind to the IGF1R albeit with considerably lower affinity as compared to the insulin receptor.

NNC0123-0327 is a liver-preferential insulin analogue with a C20 fatty diacid attached at position A22K. NNC0123-0327 is able to bind reversibly to serum albumin with high affinity (which reduces the trans-endothelial transport from plasma to periphery) while retaining a high InsR affinity in the presence of albumin compared to other acylated insulin analogues ensuring a high hepatic InsR-mediated clearance). Due to these properties, NN0123-0327 therefore displays its liver-preferential effects following peripheral administration.