MK-886

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.

Product information

CAS Number: 118414-82-7

Molecular Weight: 472.08

Formula: C27H34ClNO2S

Synonym:

L 663536

Chemical Name: 3-[3-(tert-butylsulfanyl)-1-[(4-chlorophenyl)methyl]-5-(propan-2-yl)-1H-indol-2-yl]-2, 2-dimethylpropanoic acid

Smiles: CC(C)(C)SC1C2=CC(=CC=C2N(CC2C=CC(Cl)=CC=2)C=1CC(C)(C)C(O)=O)C(C)C

InChiKey: QAOAOVKBIIKRNL-UHFFFAOYSA-N

InChi: InChI=1S/C27H34ClNO2S/c1-17(2)19-10-13-22-21(14-19)24(32-26(3,4)5)23(15-27(6,7)25(30)31)29(22)16-18-8-11-20(28)12-9-18/h8-14,17H,15-16H2,1-7H3,(H,30,31)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 75 mg/mL (158.87 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

MK-886 (0.5-2 µM; 15 hours; primary keratinocytes) treatment reduces keratin-1 expression in a culture of mouse primary keratinocytes. 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. Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists are unable to prevent MK-886-induced apoptosis.

In Vivo:

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. 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.

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.

Products are for research use only. Not for human use.