Arginase inhibitor 1 is a potent inhibitor of human arginases I and II [IC50s: 223 and 509 nM].

Arginases I:223 nM , Arginases II:509 nM

Arginase inhibitor 1 is an arginase inhibitor with significant activity in a rat model of myocardial ischemia/reperfusion injury (MI/RI). Arginase inhibitor 1 is potent against hARG I in both in vitro enzyme and cellular assays. The IC50 for Arginase inhibitor 1 is 8 μM in CHO Cells Over-Expressing hArgI

Pharmacokinetic evaluation of Arginase inhibitor 1 is conducted after intravenous (i.v.) and oral (p.o.) dosing in male Sprague-Dawley rats (n=3 per dose route). Arginase inhibitor 1 is formulated in 0.9% saline and administered intravenously at 10 mg/kg by bolus through a pre-implanted cannula at a dosing volume of 1 mL/kg, and orally at 10 mg/kg via gavage at a dosing volume of 2 mL/kg. Following i.v. dosing with 10 mg/kg in fasted animals, Arginase inhibitor 1has a terminal elimination half-life (t1/2) of 3.3 h with a volume of distribution and total body clearance of 1.86 L/kg and 7.89 mL/min/kg, respectively. The oral bioavailability of Arginase inhibitor 1 (10 mg/kg, p.o.) is 28% with a Cmax of 0.45 mg/L.