MK 886

MK 886 is a potent, cell-permeable and orally-active inhibitor of 5-lipoxygenase-activating protein (FLAP), with an IC50 value of 30 nM for inhibition of [125I]-L-691,678 photoaffinity labelling. FLAP is essential for the activation of 5-lipoxygenase (5-LO) and therefore for the biosynthesis of leukotrienes. Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in various inflammatory responses, such as asthma, arthritis as well as psoriasis. In addition, MK 886 is also a non-competitive antagonist of the peroxisome-proliferator-activated receptor alpha (PPARα), with the ability to induce apoptosis.

References:

1. Mancini JA, Prasit P, Coppolino MG, et al. 5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors. Molecular Pharmacology, 1992, 41(2): 267-272.

2.Dixon RA, Diehl RE, Opas E, et al. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature, 1990, 343(6255): 282-284.

3. Kehrer JP, Biswal SS, La E, et al. Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochemical Journal, 2001, 356(Pt 3): 899-906.

4. Imbesi M, Zavoreo I, Uz T, et al. 5-Lipoxygenase inhibitor MK-886 increases GluR1 phosphorylation in neuronal cultures in vitro and in the mouse cortex in vivo. Brain Research, 2007, 1147: 148-153.