GSK2190915 is a selective inhibitor of human 5-lipoxygenase-activating protein (FLAP; IC50 = 2.9 nM).1 It is selective for FLAP over 5-, 12-, and 15-lipoxygenase, leukotriene A4 (LTA4) hydrolase, LTC4 synthase, COX-1, and COX-2 (IC50s = >10 ?m for all). GSK2190915 inhibits production of LTB4 induced by the calcium ionophore A23187 in isolated whole blood from human, rat, and mouse (IC50s = 436, 223, and 148 nM, respectively). It decreases increases in the levels of cysteinyl leukotriene (CysLT) and LTB4 induced by lung instillation of A23187 in the bronchoalveolar lavage fluid (BALF) of rats when administered at doses of 1 and 3 mg/kg. GSK219095 (3 mg/kg) also reduces increases in the levels of CysLT, LTB4, myeloperoxidase (MPO), and plasma protein extravasation in a mouse model of peritonitis induced by zymosan in mice.
1.Lorrain, D.S., Bain, G., Correa, L.D., et al.Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammationEur. J. Pharmacol.640(1-3)211-218(2010)