MK-886

MK-886 (L 663536) is a potent, cell-permeable and orally active FLAP (IC₅₀ of 30 nM) and leukotriene biosynthesis (IC₅₀s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. MK-886 is also a non-competitive PPARα antagonist and can induce apoptosis^[1][2][3]. IC50 & Target: IC50: 30 nM (FLAP)^[3]
IC50: 3 nM (Leukotriene biosynthesis in intact leukocytes) and 1.1 μM (Leukotriene biosynthesis in human whole blood)^[2]
PPARα^[1] In Vitro: MK-886 (0.5-2 µM; 15 hours; primary keratinocytes) treatment reduces keratin-1 expression in a culture of mouse primary keratinocytes^[1].
Using a transient transfection system in monkey kidney fibroblast CV-1 cells, mouse keratinocyte 308 cells and human lung adenocarcinoma A549 cells, 10 µM MK-886 is able to inhibit Wy-14643 activation of PPARα by ~80%. MK-886 also decreases PPARα activation by fatty acids in the stable transfection system^[1].
Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists are unable to prevent MK-886-induced apoptosis^[1]. In Vivo: MK-886 (L 663536; 5 mg/kg; oral administration; male Sprague-Dawley rats) treatment potently inhibits the antigen-induced dyspnea in inbred rats pretreated with methysergide^[2].
MK-886 (L 663536) inhibits leukotriene biosynthesis in vivo in a rat pleurisy model (ED₅₀, 0.2 mg/kg p.o.), an inflamed rat paw model (ED₅₀, 0.8 mg/kg), a model of leukotriene excretion in rat bile following antigen provocation^[2].