S 50131 and S 51434, two novel small molecule glucokinase activators, lack chronic efficacy despite potent acute antihyperglycaemic activity in diabetic mice.

ABSTRACT:

Background and purpose

Small molecule glucokinase activators (GKAs) have been associated with potent antidiabetic efficacy and hepatic steatosis in rodents. This study reports the discovery of S 50131 and S 51434, two novel GKAs with an original scaffold and an atypical pharmacological profile.

Experimental approach

Activity of the compounds was assessed in vitro by measuring activation of recombinant glucokinase, stimulation of glycogen synthesis in rat hepatocytes and increased insulin secretion from rat pancreatic islets of Langerhans. Efficacy and safety in vivo were evaluated after oral administration in db/db mice by measuring glycaemia, HbA1c and dyslipidaemia-associated events.

Key results

S 50131 and S 51434 activated GK and stimulated glycogen synthesis in h

SUBMITTER: De Ceuninck F 

PROVIDER: S-EPMC3696324 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature