MK-886  (Synonyms: L 663536)

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: 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]

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

472.08

Solid

C₂₇H₃₄ClNO₂S

118414-82-7

CC(C)C1=CC=C(N(CC2=CC=C(Cl)C=C2)C(CC(C)(C(O)=O)C)=C3SC(C)(C)C)C3=C1

Room temperature in continental US; may vary elsewhere.

• [1]. [1] Kehrer JP et al. Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J. 2001 Jun 15.  [Content Brief]

  [2]. [2] Gillard J et al. 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. 1989 May;67(5):456-64.  [Content Brief]

  [3]. Mancini JA, et al. 5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors. Mol Pharmacol. 1992 Feb;41(2):267-72.  [Content Brief]