Fiboflapon (GSK2190915) is an orally available and effective 5-lipoxygenase-activating protein (FLAP) inhibitor that binds FLAP with a titer of 2.9 nM and inhibition of LTB4 in human blood with an IC50 of 76 nM.

LTB4:76 nM

Fiboflapon (AM-803) demonstrates excellent preclinical toxicology and pharmacokinetics in both rats and dogs. In the rodent bronchoalveolar lavage (BAL) model, Fiboflapon (AM-803) also exhibits prolonged pharmacological effects[2].

Orally administered at 1 mg/kg, Fiboflapon (AM-803) sustains a continuous inhibition of ex vivo ionophore-stimulated whole blood leukotriene B4 (LTB4) biosynthesis, with an inhibition rate exceeding 90% for up to 12 hours, and an EC50 of approximately 7 nM. When rat lungs are subjected to in vivo calcium ionophore challenge, Fiboflapon (AM-803) inhibits the production of LTB4 and cysteinyl leukotrienes (CysLT) with ED50 values of 0.12 mg/kg and 0.37 mg/kg, respectively. Following a single oral dose of 3 mg/kg, the inhibition rates measured 16 hours later for LTB4 and CysLT are 86% and 41%, respectively. In an acute inflammatory environment, Fiboflapon dose-dependently reduces LTB4, CysLT, plasma protein extravasation, and neutrophil influx induced by intraperitoneal yeast glucan injection. Lastly, Fiboflapon increases the survival time of mice exposed to intravenous injection of lethal platelet-activating factor (PAF) [2].