AR453588

Biological Activity

AR453588 is a potent and orally bioavailable anti-diabetic glucokinase activator, with an EC50 of 42 nM. AR453588 shows anti-hyperglycemic activity[1]. AR453588 (3-30 mg/kg; p.o) lowers post-prandial glucose in normal C57BL/6J mice[1].AR453588 (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 (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 (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].

References

[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.