Arginase inhibitor 1

1345808-25-4

C13H27BN2O4

H2O : >= 30 mg/mL (104.83 mM); DMSO : >= 48 mg/mL (167.73 mM)

Immunology/Inflammation; Metabolic Enzyme/Protease

Arginase inhibitor 1 is a potent inhibitor of human arginases I and II with IC₅₀s of 223 and 509 nM, respectively. IC50 & Target: IC50: 223 nM (arginases I), 509 nM (arginases II)^[1] In Vitro: Arginase inhibitor 1inhibits human arginases I and II with IC₅₀s of 223+/-22.3 and 509+/-85.1 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). Arginase inhibitor 1 is a novel second generation 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 uM in CHO Cells Over-Expressing hArgI^[1]. In Vivo: A 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 preimplanted 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 (t_1/2) 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 C_max of 0.45 mg/L^[1].