RO0274375

RO0274375 is a small molecule allosteric activator of glucokinase (GK), developed by Roche as a lead compound for the treatment of type 2 diabetes mellitus. It is the racemic form of a propionamide derivative, with its (R)-enantiomer designated as RO0281675. RO0274375 acts as a 'glucose sensor' enhancer by binding to an allosteric site on glucokinase, thereby increasing the enzyme's affinity for glucose. This mechanism results in stimulated insulin secretion from pancreatic beta cells and enhanced glucose metabolism and glycogen synthesis in the liver. Although RO0274375 and its enantiomer were pivotal in validating glucokinase as a therapeutic target, they were primarily used as tool compounds and leads in the structure-activity relationship (SAR) development that eventually led to clinical candidates like piragliatin. Development of this specific racemic compound was not pursued to late-stage clinical trials.

Other names

3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide