glucokinase in human

PF-04991532 is an effective, hepatoselective glucokinase activator. It has EC50s of 80 and 100 nM in human and rat, respectively.

GKA-22 is a human glucokinase allosteric activator in the absence of glucose.

GKA50 quarterhydrate is a potent glucokinase activator with an EC50 value of 33 nM. This glucose-like activator of β-cell metabolism in rodent and human pancreatic islets is a Ca2+-dependent regulator of insulin secretion. It stimulates insulin secretion in mouse islets and significantly reduces blood glucose in high-fat-fed female rats.

ARRY-403, also known as AMG-151, is an orally available allosteric glucokinase (GK) activator developed for the treatment of type 2 diabetes mellitus (T2DM). ARRY-403 has many favorable physicochemical characteristics and ADME properties (low potential to cause drug–drug interactions (DDIs). ARRY-403 potently activates human glucokinase (GK) in vitro (EC50 = 79 nM at 5 mM glucose), with an S0.5 = 0.93 mM glucose (ARRY-403 at 5 mM) and Vmax = 134% compared to the no activator control. It possesses good in vitro drug-like properties (aqueous solubility, cell permeability, low low potential for drug-drug interactions, low predicted hepatic clearance), and selectivity against broad panels of receptors and enzymes.