PSN-GK1

PSN-GK1 is a potent glucokinase activator with an EC₅₀ of 0.13 μM. IC50 & Target: EC50: 0.13 μM^[1] In Vivo: PSN-GK1 exhibits an excellent pharmacokinetic profile, with high oral bioavailability, in the rat. PSN-GK1 can markedly reduce blood glucose which accompanied by a trend toward increased pancreatic insulin release. Separately, the antihyperglycemic actions of PSN-GK1 have been shown to be a result of both pancreatic and hepatic effects. In addition, PSN-GK1 engenders potent antihyperglycemic effects in diabetic rodents without causing hypoglycemia^[1]. At 5 mM glucose, PSN-GK1 activates glucokinase (4.3-fold, EC₅₀=130 nM), increases MIN6 insulin secretion (26-fold, EC₅₀=267 nM) and 2-DG hepatocytic uptake (3-fold, EC₅₀=1 μM). In C57Bl/6 mice, PSN-GK1 reduces blood glucose at 1 and 10 mg/kg (by mouth), but insulin is increased significantly at only the higher dose. In hyperinsulinaemic 10-mM glucose clamps, PSN-GK1 increases2-DG incorporation into liver glycogen sixfold, directly demonstrating liver effects^[2].