In Vitro: ASB14780 shows selectivity to cPLA2α (IC50 =20 nM) over type II sPLA2 (IC50 >10 μM). 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.
In Vivo: TPA (tetradecanoyl phorbol acetate) causes acute inflammation with ear, resulting in edema. 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. 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. 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.). Oral Bioavailabilities and Pharmacokinetic Parameters of ASB14780