ASB14780 (C005B-311481)

Biochem/physiol Actions

ASB14780 can be a potential therapeutic for the treatment of asthma and other pulmonary diseases. In addition, its inhibitory function on group IVA phospholipase A2 (IVA-PLA2) qualifies this drug to be a potential candidate for the treatment of non-alcoholic fatty liver diseases.

ASB14780 is an indole-based selective and potent cytosolic phospholipase A₂α inhibitor (IC₅₀ = 20 nM/cPLA₂α and >10 μM/sPLA₂α). ASB14780 inhibits cPLA₂α-dependent inflammatory responses both in cultures and in animals in vivo, including LPS-induced PGE2 production (IC₅₀ = 0.5 μM; mouse peritoneal exudate cells), A23187-induced TXB2 production (IC₅₀ = 0.54 and 0.64 μM using guinea pig and human whole blood, respectively), TPA-induced ear edema (50 mg/kg, p.o.; mice), OVA-induced asthma (5 - 20 mg/kg/d, p.o.; guinea pig), CCl4-induced hepatic fibrosis and high-fat cholesterol diet-induced fatty liver (0.1-0.3 g/kg/d, p.o.; mouse). SB14780 bioavailability is also demonstrated in dog and monkey, albeit at a lower value (F = 34.3%/dog and 30.9%/monkey vs. 89.6%/mouse).