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.
性状
Solid
IC50 & Target[1][2]
IC50: 30 nM (FLAP)
IC50: 3 nM (Leukotriene biosynthesis in intact leukocytes) and 1.1 μM (Leukotriene biosynthesis in human whole blood)
PPARα
体外研究(In Vitro)
MK-886 (0.5-2 μM; 15?hours; primary keratinocytes) treatment reduces keratin-1 expression in a culture of mouse primary keratinocytes.
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.
Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists are unable to prevent MK-886-induced apoptosis.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis
Cell Line:
Primary keratinocytes
Concentration:
0.5 μM, 1 μM or 2 μM
Incubation Time:
15?hours
Result:
Decreased in keratin-1 expression.
体内研究(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.
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.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Sprague-Dawley rats (300-400 g) with antigen-induced dyspnea