Glucokinase activator 1

Glucokinase activator 1 is a liver-directed glucokinase activator with an EC50 of 34 nM.

Signaling Pathways >> Metabolic Enzyme/Protease >> Glucokinase

Research Areas >> Metabolic Disease

EC50: 34 nM (Glucokinase)[1]

Glucokinase activator 1 (3 to 300 mg/kg, oral, 180 minutes) shows a dose dependent improvement in glucose excursion in oGTT in a DIO mouse model of T2D. The predominant liver-directed tissue distribution of Glucokinase activator 1 ensures a good safety window with respect to hypoglycemia over a 10-fold dose range[1]. Animal Model: Male C57BL/6J mice (age 8-10 weeks; 25±5 g)[1] Dosage: 1 or 3 mg/kg (i.v.), 30 mg/kg (oral) Administration: i.v. or oral Result: Glucokinase activator 1 shows an excellent PK profile and exhibited 35- and 68- fold higher liver concentrations at 1 and 3 h time point, respectively, compared with plasma[1]. Animal Model: Male C57BL/6J mice of 10-12 weeks[1] Dosage: 3 to 300 mg/kg Administration: Oral (15, 30, 60, 120 and 180 minutes) Result: Glucokinase activator 1 demonstrates 21% and 34% significant AUCglucose reduction at oral dose of 30 and 100 mg/kg, respectively[1].

[1]. Deshpande AM, et al. Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia. Eur J Med Chem. 2017 Jun 16;133:268-286.