Description
MK-886 (118414-82-7) is an inhibitor of leukotriene biosynthesis(IC50 = 2.5 nM in human PMN)1 via 5-lipoxygenase-activating protein (FLAP) inhibition (IC50 = 30 nM)2. MK-886 also inhibits PPARα (80% inhibition at 10 μM).3
Chemical Properties
White Solid
Uses
Binds to 5-lipoxygenase-activating protein with high affinity and prevents the activation of 5-lipoxygenase, thus inhibiting the biosynthesis of leukotrienes.
Uses
MK-886 is a potent and selective inhibitor of FLAP and Cox-1.
Definition
ChEBI: A member of the class of indoles that is 1H-indole substituted by a isopropyl group at position 5, a tert-butylsulfanediyl group at position 3, a 4-chlorobenzyl group at position 1 and a 2-carboxy-2-methylpropyl group at pos
tion 2. It acts as an inhibitor of arachidonate 5-lipoxygenase.
Biological Activity
An inhibitor of leukotriene biosynthesis (IC 50 = 3 nM in human polymorphonuclear leukocytes). Acts by inhibiting 5-lipoxygenase-activating protein (FLAP) (IC 50 = 30 nM for inhibition of [ 125 I]-L-691,678 photoaffinity labelling). Also moderately potent PPAR α antagonist (IC 50 = 0.5-1 μ M). Orally active in vivo .
References
References/Citations
1) Gillard et al (1989) L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor; Can. .J. Physiol .Pharmacol. 67 456
2) Evans et al (1991) 5-Lipoxygenase-activating protein is the target of a quinoline class of leukotriene synthesis inhibitors; Mol. Pharmacol. 40 22
3) Kehrer et al (2001) Inhibition of peroxisome-proliferator-activated receptor (PPAR)α by MK886; Biochem. J. 356 899
