AR453588 hydrochloride

AR453588 hydrochloride is a potent and orally bioavailable anti-diabetic glucokinase activator, with an EC50 of 42 nM. AR453588 hydrochloride shows anti-hyperglycemic activity[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> Glucokinase

Research Areas >> Metabolic Disease

AR453588 hydrochloride (3-30 mg/kg; p.o) lowers post-prandial glucose in normal C57BL/6J mice[1]. AR453588 hydrochloride (3-30 mg/kg; p.o.; once-daily for 14 days) shows anti-hyperglycemic activity in a dose-ranging 14 day ob/ob mouse[1]. AR453588 hydrochloride (10 mg/kg; p.o.) treatment shows that the Tmax, AUCinf, Vss, Cmax and F are 1.0 mL/min/kg, 4.65 h μg /mL, 1.67 μg /mL and 60.3%, respectively[1]. AR453588 hydrochloride (1 mg/kg; i.v.) treatment shows that the CL, AUCinf, Vss, and t1/2 are 21.6 mL/min/kg, 0.77 h μg /mL, 0.746 L/kg and 1.28 hours, respectively[1]. Animal Model: Male diabetic ob/ob mice[1] Dosage: 3, 10, 30 mg/kg Administration: Orally once-daily for 14 days Result: Lowered the fasted blood glucose from the control animals on day 14 as well as the AUC of the OGTT (oral glucose tolerance tests). Animal Model: Male CD-1 mice[1] Dosage: 10 mg/kg Administration: p.o. (Pharmacokinetic Analysis) Result: The Tmax, AUCinf, Vss, Cmax and F were 1.0 mL/min/kg, 4.65 h μg /mL, 1.67 μg /mL and 60.3%, respectively

[1]. Hinklin RJ, et al. Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator. Bioorg Med Chem. 2020 Jan 1;28(1):115232.