MK591

Short Summary : FLAP inhibitor,potent and selective

Category : Others|FLAP

Purity : 0.98

CAS Number : 147030-01-1

Formula : C34H34ClN2NaO3S

Molecular Weight : 609.15

SMILE : CC(C)(C)SC1=C(N(C2=C1C=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)CC5=CC=C(C=C5)Cl)CC(C)(C)C(=O)[O-].[Na+]

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description :
IC50: 1.6 nM in a FLAP binding assay for MK-0591, which is the acid form of MK591 [1]
Arachidonate 5-lipoxygenase-activating protein is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes. MK-591 (MK-0591 sodium) is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor.
In vitro: A series of performed inhibitor studies identified a specific inhibitor of 5-LO (MK-591), which has the ability to block JNK, MAPK and 5-LO signaling-cascades and drastically reducing the activity of pro-inflammatory cytokine TNF-a. Further evaluation of MK-591 utilizing cell proliferation assays in PBMCs, human proximal tubule cells showed a decrease in cell proliferation [2].
In vivo: Amyloid peptide (A) deposition in the brains of mice receiving MK-591 was significantly reduced when compared with controls. MK-591 treatment did not cause any change in the steady-state levels of-site amyloid precursor protein cleaving enzyme 1, amyloid- precursor protein or disintegrin and metalloproteinase domain-containing protein 10. By contrast, MK-591 caused a significant reduction of the -secretase complex, at the protein and message level [3].
Clinical trial: In an open-label and pilot study, short-term therapy with MK-591 reduces proteinuria by restoring glomerular size selectivity and thus reduces transglomerular protein trafficking. These benefits may result from glomerular leukotriene biosynthesis inhibition, but other MK-591-specific actions cannot be excluded [4].
References:[1] Brideau C, Chan C, Charleson S, Denis D, Evans JF, Ford-Hutchinson AW, Fortin R, Gillard JW, Guay J, Guvremont D, et al. Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5- (quinolin-2-yl-methoxy)-indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1992;70(6):799-807.[2] Mendis C, Campbell K, Das R, Yang D, Jett M. Effect of 5-lipoxygenase inhibitor MK591 on early molecular and signaling events induced by staphylococcal enterotoxin B in human peripheral blood mononuclear cells. FEBS J. 2008;275(12):3088-98. [3] Jin Chu and Domenico Pratic. Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimers disease mouse model. J Neuroinflammation. 2012; 9: 127. [4] Guasch A, Zayas CF, Badr KF. MK-591 acutely restores glomerular size selectivity and reduces proteinuria in human glomerulonephritis. Kidney Int. 1999;56(1):261-7.

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