RO-28-1675 is a direct and selective glucokinase activator that indirectly affects the activity of the GK/GKRP (glucokinase regulatory protein) complex, with efficacy decreasing with increasing glucose concentration, and can be used in studies related to insulin secretion and type 2 diabetes.

GK:54 nM (EC50)

In experiments with rat islet (Langerhans islet) cells and primary rat hepatocytes, RO-28-1675 showed an effect on the nuclear-cytoplasmic transport of glucokinase (GCK) in hepatocytes. Additionally, RO-28-1675 (3 μM) was able to lower the glucose concentration threshold required to stimulate insulin secretion. This suggests that RO-28-1675 not only regulates the subcellular localization of GCK but also enhances the glucose sensitivity of islet cells, thereby promoting insulin secretion [1].

In a diabetic mouse model with a Gck gene mutation, oral administration of RO-28-1675 (50 mg/kg) induced hypoglycemia in wild-type mice [2]. Pharmacokinetic studies indicated that RO-28-1675 has excellent absorption properties, with an oral bioavailability of 92.8% in mice. After a single dose of 10 mg/kg, the peak plasma concentration (Cmax) reached 1140 μg/mL [3].