Fiboflapon sodium (GSK2190915) is an orally bioavailable 5-lipoxygenase-activating protein (FLAP) inhibitor with a potency of 2.9 nM in FLAP binding, an IC50 of 76 nM for inhibition of LTB4 in human blood.

LTB4:76 nM

In vivo studies revealed that Fiboflapon (AM803) effectively inhibits the production of LTB4 and cysteinyl leukotriene (CysLT) in rat lungs challenged with calcium-ionophore, showing ED50 values of 0.12 mg/kg and 0.37 mg/kg, respectively. Following a single oral dose of 3 mg/kg, inhibition levels 16 hours post-administration were 86% for LTB4 and 41% for CysLTs. In scenarios of acute inflammation, Fiboflapon (AM803) demonstrated a dose-dependent reduction in LTB4, CysLTs, plasma protein extravasation, and neutrophil influx following peritoneal zymosan injection. Furthermore, AM803 significantly prolonged survival in mice after a lethal dose of platelet-activating factor (PAF) intravenously. Fiboflapon (AM803) has shown excellent preclinical toxicology and pharmacokinetics in rats and dogs, alongside a remarkable pharmacodynamic extension in a rodent bronchoalveolar lavage (BAL) model. Oral administration at 1 mg/kg led to a sustained inhibition of LTB4 biosynthesis in ex vivo ionophore-challenged whole blood, with over 90% inhibition lasting up to 12 hours and an EC50 of approximately 7 nM.