MK-886 (sodium salt)

Names

[ Name ]:
MK-886 (sodium salt)

[Synonym ]:
MK-886 sodium salt hydrate
Sodium 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-isopropyl-1H-indol-2-yl]-2,2-dimethylpropanoate
Lopac-M-2692
1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-α,α-dimethyl-5-(1-methylethyl)-, sodium salt (1:1)
MK-886 sodium salt
MK-886
Sodium 3-{1-(4-chlorobenzyl)-5-isopropyl-3-[(2-methyl-2-propanyl)sulfanyl]-1H-indol-2-yl}-2,2-dimethylpropanoate
MK-886 sodium hydrate

Biological Activity

[Description]:

MK-886 (L 663536) sodium salt 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 sodium salt is also a non-competitive PPARα antagonist and can induce apoptosis[1][2][3].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> FLAP

Signaling Pathways >> GPCR/G Protein >> Leukotriene Receptor

Signaling Pathways >> Cell Cycle/DNA Damage >> PPAR

[Target]

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]

[In Vitro]

MK-886 sodium salt (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 sodium salt is able to inhibit Wy-14643 activation of PPARα by ~80%. MK-886 sodium salt 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 sodium salt-induced apoptosis[1].

[In Vivo]

MK-886 sodium salt (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 sodium salt (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].

[References]

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

[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.

[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.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₇H₃₃ClNNaO₂S

[ Molecular Weight ]:
494.06

[ Exact Mass ]:
493.181824

[ PSA ]:
70.36000

[ LogP ]:
6.67560

MSDS

Click to get detail MSDS

Related Compounds

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