ARN14974

ARN14974, a benzoxazolone carboxamide, is a potent and systemically active inhibitors of intracellular acid ceramidase (IC₅₀=79 nM)^[1]. In Vitro: ARN14974 (20 μM; 24 hours; SW403 and Raw 264.7 cells) inhibits acid ceramidase (AC) in a complex cellular environment, leading to the intended biochemical response, that is, increased ceramide and decreased sphingosine levels^[1]. In Vivo: ARN14974 (10 mg/kg; i.p.; mice) causes a substantial reduction in AC activity in multiple organs, including brain, liver, heart, lungs, and kidney^[1].
ARN14974 (10 mg/kg; i.p.) quickly enters the bloodstream after a single intraperitoneal administration in mice, reaching a maximal plasma concentration, C_max, of 1767.9 ng/mL and displaying a half-life time of 458 min in circulation. ARN14974 (1 mg/kg; i.v.) shows a C_max and a half-life time of 628 ng/mL and 72 min, respectively^[1].