Table 1.

Effects of IDE inhibitors on insulin clearance. n.d. = not determined. ^a From experiments in mice, unless otherwise indicated.

Compound	Ki/IC50 Value	Mechanism	Effects on Insulin Levels a	Insulin Clearance a	Refs.
Ii1	Ki = ~16 nM (insulin)	Zn-targeting and stabilizing closed conformation	Blocked degradation of extracellular insulin by CHO-IR and HeLa cells	n.d.	[168]
6bk	IC50 = ~100 nM (insulin)	Steric blockade of internal chamber	Elevated plasma insulin after IP insulin or glucose administration	n.d.	[166]
NTE-1	IC50 = ~4 nM (insulin) IC50 = ~3 nM (glucagon)	Steric blockade of internal chamber	No significant effect on plasma insulin levels	No effect	[173]
NTE-2	IC50 = ~4 nM (insulin) IC50 = ~150 nM (glucagon)	Steric blockade of internal chamber	No effect on extracellular insulin degradation by HEK293 cells	Little effect in HEK293 cells	[173]
BMD44768	Ki = ~60 nM (insulin)	Zn-targeting and stabilizing closed conformation	Elevated plasma insulin after exogenous insulin administration	n.d.	[174]
B35	IC50 = ~22 nM (insulin)	Active-site blockade; mimics insulin B chain sequence that binds to active site	Elevated basal plasma insulin levels Increased levels of insulin 120 min after IP injection of B35	n.d.	[178]
ML345	IC50 = ~23 nM (insulin)	Quasi-irreversible Cys-targeting; selectively inhibits IDE in oxidized environment	n.d.	n.d.	[180]
P12-3A	Ki = ~2,5 uM (insulin)	Steric blockade of active site	Blocked degradation of extracellular insulin in fibroblasts	Inhibitory effect in cultured fibroblast	[181]
BRD8283	IC50 = ~100 nM (insulin)	Binding to the IDE exosite region uniquely occupied by insulin	n.d.	n.d.	[185]