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Endocrine/metabolic disease


Insulin degrading enzyme (IDE)

Mouse and in vitro studies suggest inhibiting IDE could help treat type 2 diabetes. Library screening, chemical synthesis and in vitro testing identified a macrocyclic compound that bound to a noncatalytic site of IDE and inhibited the enzyme with a nanomolar IC50 value. In a mouse model of diet-induced obesity, i.p. delivery of the compound increased liver and plasma levels of insulin, glucagon and amylin compared with vehicle. The compound also increased the duration of amylin-regulated gastric emptying and improved glucose tolerance. Next steps could include evaluating the compound in other models of type 2 diabetes.

SciBX 7(24); doi:10.1038/scibx.2014.711
Published online June 19, 2014

Patent application filed; unlicensed

Maianti, J.P. et al. Nature;
published online May 21, 2014;
Contact: David R. Liu, Harvard University, Cambridge, Mass.