AMG-1694 is a potent glucokinase–glucokinase regulatory protein (GK-GKRP) disruptors and promotes the dissociation of the GK-GKRP complex with an IC50 of 7 nM, indirectly increasing GK enzymatic activity. AMG-1694 potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation. AMG-1694 normalizes blood glucose levels in several rodent models of diabetes and lowes blood glucose restricted to diabetic and not normoglycaemic animals.
AMG-1694 is highly effective in restoring the enzymatic activity of GK with an EC50 of 0.020 μM in the presence of GKRP[1].
References:
[1]. Lloyd DJ, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40.