MK-886是一种细胞可渗透的，具有口服活性的 FLAP (IC50为 30 nM) 和白三烯生物合成 (完整白细胞和人全血中的IC50分别为 3 nM 和 1.1μM) 的抑制剂。它也是一种非竞争性PPARα拮抗剂，可以诱导细胞凋亡。

MK-886 is an inhibitor of leukotriene biosynthesis, inhibiting 5-lipoxygenase-activating protein (FLAP). It is also a moderately potent PPARα antagonist.

MK-886, an inhibitor of the 5-lipoxygenase-activating protein (FLAP), potently suppresses leukotriene biosynthesis in intact cells and is frequently used to define a role of the 5-lipoxygenase (EC 1.13.11.34) pathway in cellular or animal models of inflammation, allergy, cancer, and cardiovascular disease. MK-886 inhibits isolated COX-1 (IC50=8 μM) and blocks the formation of the COX-1-derived products 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid (12-HHT) and thromboxane B2 in washed human platelets in response to collagen as well as from exogenous arachidonic acid (IC50=13–15 μM).Isolated COX-2 was less affected (IC50=58 μM), and in A549 cells, MK-886 (33 μM) failed to suppress COX-2-dependent 6-ketoprostaglandin (PG)F1α formation. MK-886 (10 μM) inhibits COX-1-mediated platelet aggregation induced by collagen or arachidonic acid whereas thrombin- or U-46619-induced (COX-independent) aggregation is not affected[1].

Repeated daily i.p. injections of MK-886 results in increased GluR1 phosphorylation in brain samples obtained from the prefrontal cortex. In contrast, a single injection of MK-886 does not alter cortical GluR1 phosphorylation[2].

Enzyme assay is conducted in buffer containing 25 mM Tris, pH 8.0, 1 mM DTT, 1 mM spermine, 50 mM KCl, 0.01% Nonidet P-40, and 1 mM MgCl2. PARP reaction contains 0.1 μCi [3H]NAD+ (200 000 DPM), 1.5 μM NAD+, 150 nM biotinylated NAD+, 1 μg/mL activated calf thymus, and 1?5 nM PARP-1. Autoreactions utilizing SPA bead-based detection are carried out in 50 μL volumes in white 96-well plates. Compounds (e.g., MK-4827) are prepared in 11-point serial dilution in 96-well plate, 5 μL/well in 5% DMSO/Water (10× concentrated). Reactions are initiated by adding first 35 μL of PARP-1 enzyme in buffer and incubating for 5 min at room temperature and then 10 μL of NAD+ and DNA substrate mixture. After 3 h at room temperature, these reactions are terminated by the addition of 50 μL of streptavidin-SPA beads (2.5 mg/mL in 200 mM EDTA, pH 8). After 5 min, they are counted using a TopCount microplate scintillation counter. IC50 data is determined from inhibition curves at various substrate concentrations[1].

IL-1β-stimulated A549 cells (5×106/ml) are pre-incubated with MK-886 (MK, 33 μM), indomethacin (Indo, 10 μM), celecoxib (Cele, 5 μM) or vehicle (DMSO) for 15 min prior to the addition of 30 μM arachidonic acid. After 15 min at 37 °C, the amount of released 6-keto PGF1α was assessed by ELISA as described in the Materials and methods section. (Only for Reference)

118414-82-7

C27H34ClNO2S

472.08

L 663536;MK886

Ethanol:2.4 mg/mL (5 mM)
DMSO:47.2 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years