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Biochem Biophys Res Commun. 2008 Nov 14;376(2):380-3. doi: 10.1016/j.bbrc.2008.08.151. Epub 2008 Sep 7.

A novel high-affinity peptide antagonist to the insulin receptor.

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Diabetes Research Unit, Novo Nordisk A/S, Novo Nordisk Park G8.1.77, DK-2760 Maaloev, Denmark.


In this publication we describe a peptide insulin receptor antagonist, S661, which is a single chain peptide of 43 amino acids. The affinity of S661 for the insulin receptor is comparable to that of insulin and the selectivity for the insulin receptor versus the IGF-1 receptor is higher than that of insulin itself. S661 is also an antagonist of the insulin receptor of other species such as pig and rat, and it also has considerable affinity for hybrid insulin/IGF-1 receptors. S661 completely inhibits insulin action, both in cellular assays and in vivo in rats. A biosynthetic version called S961 which is identical to S661 except for being a C-terminal acid seems to have properties indistinguishable from those of S661. These antagonists provide a useful research tool for unraveling biochemical mechanisms involving the insulin receptor and could form the basis for treatment of hypoglycemic conditions.

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