Over the last decade, numerous compounds that activate glucokinase have advanced into the clinic to treat diabetes, but the approach has faced safety challenges because of, amongst other issues, high rates of adverse hypoglycemic events. Now, researchers from Amgen Inc. have identified compounds that instead target glucokinase regulator, opening the door to a potentially safer strategy for modulating hepatic glucokinase activity.1
Glucokinase (GCK; GK) catalyzes the conversion of glucose into glucose-6-phosphate, the first step of glycolysis, and is a key regulatory component for maintaining homeostatic levels of glucose in humans. Most of the enzyme is concentrated in the liver, but it also plays a key role in glucose sensing in the pancreas.
Since Roche scientists described the first allosteric GK activator a decade ago,2 diverse classes of compounds have been synthesized and advanced into the clinic