InsR peptide antagonist (S961)

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 InsR.

NNC0069-0961 (also known as S961) is a single chain peptide consisting of 43 amino acids, which has been shown to be a specific InsR antagonist. The affinity of S961 for the InsR is comparable to that of human insulin and the selectivity for the insulin receptor versus the IGF1 receptor is higher than that of human insulin. S961 is also an antagonist of the InsR of other species such as pig and rat and it also has considerable affinity for hybrid receptors consisting of InsR and IGF1R. S961 completely inhibits insulin action, both in cellular in vitro assays and in vivo in rats.

Thus, S961 exhibit high affinity and selectivity for the InsR and can be used to unravel the role of InsR signaling and function in both in vivo and in vitro experiments.