Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.

ABSTRACT: Glucokinase (GK) catalyzes the phosphorylation of glucose to glucose-6-phosphate. We present the structure-activity relationships leading to the discovery of AM-2394, a structurally distinct GKA. AM-2394 activates GK with an EC50 of 60 nM, increases the affinity of GK for glucose by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, and lowers glucose excursion following an oral glucose tolerance test in an ob/ob mouse model of diabetes.

SUBMITTER: Dransfield PJ 

PROVIDER: S-EPMC4948016 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature