Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite showing effective blood glucose lowering, few pan-GKAs – acting both in pancreas and liver – have been discontinued from early clinical trials mainly because of their issues causing hypoglycemia due to over sensitization of pancreatic GK and therefore insulin secretion even at below normal glucose level. Liver-directed GKAs are believed to spare pancreatic GK and therefore would not have concern of hypoglycemia. We report here discovery of a liver-directed lead candidate, which showed anti-hyperglycemic effect in an oral glucose tolerance test (oGTT) performed in diet-induced obese (DIO) mice while showing no sign of hypoglycemia in normal C57 mice even when administered at fasted condition.

Discovery of a liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemic potential

251st National Meeting (2016)

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