ASB14780

ASB14780 is a 4-phenoxy derivative, the cytosolic Phospholipase A₂α (cPLA₂α) inhibitor, with an IC₅₀ value of 20 nM^[1]. IC50 & Target: IC50: 20 nM (cPLA2α); 0.54 μM (guinea pig cPLA2α); 0.64 μM (human cPLA2α)^[1] In Vitro: ASB14780 shows selectivity to cPLA2α (IC₅₀ =20 nM) over type II sPLA2 (IC₅₀ >10 μM)^[1].
ASB14780 (30 min pre-incucation) inhibits cPLA2α in guinea pig whole blood (GWB) and human whole blood (HWB) in a species-derived differences, with IC₅₀s of 0.54 μM and 0.64 μM, respectively, 15 min after being stimulated by 5 μM calcium ionophore A23187^[1]. In Vivo: TPA (tetradecanoyl phorbol acetate) causes acute inflammation with ear, resulting in edema^[1].
ASB14780 (50 mg/kg; p.o.; once) suppresses the increase in the ear thickness elicited by the application of TPA (tetradecanoyl phorbol acetate) in mouse^[1].
ASB14780 (5 mg/kg; 20 mg/kg; p.o.; once daily) attenuates AHR (airway hyperreactivity), and inhibits IAR (immediate asthmatic response) and LAR (late asthmatic response) in a dose-dependent manner^[1].
ASB14780 shows well oral activity of 89.6% in mouse calculated from the ratio of oral administration’s AUC (10 mg/kg; p.o.) and intravenonous administration’s AUC (1 mg/kg; i.v.)^[1].
Oral Bioavailabilities and Pharmacokinetic Parameters of ASB14780^[1]

Model	F (%)	AUC (h?μg/mL)	Cmax (μg/mL)
mouse	89.6	7.12	5.12
dog	34.3	17.1	4.96
monkey	30.9	4.96	2.29

Note: Based on 10 mg/kg p.o. dosing data.