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Chemical Compound Review

Quiflapon     3-[1-[(4- chlorophenyl)methyl]-5- (quinolin...

Synonyms: CHEMBL16596, SureCN502947, CS-0953, MK-0591, CHEBI:117620, ...
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Disease relevance of MK 0591


High impact information on MK 0591

  • Importantly, experiments with the 5-LO-activating protein inhibitor MK-0591 and the intracellular Ca2+ chelator BAPTA-AM demonstrated that the AA-regulated 5-LO translocation is FLAP- and Ca2+-dependent [4].
  • RESULTS: Montelukast and MK-0591 decreased eosinophil migration promoted by 5-oxo-ETE, whereas LTD(4) failed to induce eosinophil migration [5].
  • The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergen-induced airway responses in asthmatic subjects in vivo [6].
  • Both the EAR and the LAR were significantly reduced after administration of MK-0591 as compared with placebo, with a mean inhibition of 79% (p = 0.011) and 39% (p = 0.040), respectively [6].
  • Pharmacokinetics of MK-0591 were linear, with a half-life of approximately 6 hours [7].

Biological context of MK 0591

  • We used the 5-lipoxygenase-activating protein (FLAP) antagonist MK-0591 to investigate the importance of leukotrienes (LT) in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs [8].
  • These results indicate that peptidoleukotrienes are produced during ozone inhalation and that MK-0591 inhibits LT production in dogs [8].
  • 2. After the single-dose administration following overnight fasting, Cmax and AUC of MK-0591 in plasma increased in a dose-dependent manner, while elimination half-life remained constant (11.2-13.2 h) irrespective of dose [9].
  • MK-0591 has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands [10].

Anatomical context of MK 0591


Associations of MK 0591 with other chemical compounds


Gene context of MK 0591

  • The results show that AA- and LTB(4)-induced PLD activation were inhibited by the LTB(4) receptor 1 (BLTR1) antagonist CP 105,696, whereas the LTA(4) hydrolase inhibitor SC57461A and the LT biosynthesis inhibitor MK-0591 inhibited AA- but not LTB(4)-mediated PLD activation [17].
  • At the concentration of 1 microM, MK-0591 had no inhibitory effect on 15-lipoxygenase activity in human polymorphonuclear leukocytes, nor on human platelet 12-lipoxygenase and cyclooxygenase [13].
  • Solid dispersions of crystalline MK-0591 with PVP homopolymers of different molecular weights (2500-1 x 10(6) g/mol) and with a copolymer containing poly(vinyl acetate) (PVA), (PVP/VA, 60:40, 5.8 x 10(4) g/mol) were prepared by the solvent method [15].

Analytical, diagnostic and therapeutic context of MK 0591

  • Concentrations of LTs and other eicosanoids in bronchoalveolar lavage fluid from vehicle-treated DAC airways were increased above baseline values; only LTs were reduced by MK-0591 [11].
  • This result suggests that additional factors other than the reduction in mobility affect the crystallization behavior of MK-0591 in the solid dispersions, such as specific interactions [15].
  • On one day, dogs were treated with MK-0591 (2 mg/kg iv) followed by a continuous intravenous infusion of 8 [8].


  1. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis. Hillingsø, J., Kjeldsen, J., Laursen, L.S., Lauritsen, K., von Spreckelsen, S., Depré, M., Friedman, B.S., Malmström, K., Shingo, S., Bukhave, K. Clin. Pharmacol. Ther. (1995) [Pubmed]
  2. Inhibition of leukotriene biosynthesis improves renal function in experimental glomerulonephritis. Petric, R., Ford-Hutchinson, A. Journal of lipid mediators and cell signalling. (1995) [Pubmed]
  3. A new class of leukotriene biosynthesis inhibitor: the development of MK-0591. Prasit, P., Belley, M., Blouin, M., Brideau, C., Chan, C., Charleson, S., Evans, J.F., Frenette, R., Gauthier, J.Y., Guay, J. Journal of lipid mediators. (1993) [Pubmed]
  4. Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. Flamand, N., Lefebvre, J., Surette, M.E., Picard, S., Borgeat, P. J. Biol. Chem. (2006) [Pubmed]
  5. Montelukast regulates eosinophil protease activity through a leukotriene-independent mechanism. Langlois, A., Ferland, C., Tremblay, G.M., Laviolette, M. J. Allergy Clin. Immunol. (2006) [Pubmed]
  6. The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergen-induced airway responses in asthmatic subjects in vivo. Diamant, Z., Timmers, M.C., van der Veen, H., Friedman, B.S., De Smet, M., Depré, M., Hilliard, D., Bel, E.H., Sterk, P.J. J. Allergy Clin. Immunol. (1995) [Pubmed]
  7. Pharmacokinetics and pharmacodynamics of multiple oral doses of MK-0591, a 5-lipoxygenase-activating protein inhibitor. Depré, M., Friedman, B., Van Hecken, A., de Lepeleire, I., Tanaka, W., Dallob, A., Shingo, S., Porras, A., Lin, C., de Schepper, P.J. Clin. Pharmacol. Ther. (1994) [Pubmed]
  8. Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs. Stevens, W.H., Lane, C.G., Woolley, M.J., Ellis, R., Tagari, P., Black, C., Ford-Hutchinson, A., O'Byrne, P.M. J. Appl. Physiol. (1994) [Pubmed]
  9. Pharmacokinetic and pharmacodynamic analysis of a novel leukotriene biosynthesis inhibitor, MK-0591, in healthy volunteers. Uematsu, T., Kanamaru, M., Kosuge, K., Hara, K., Uchiyama, N., Takenaga, N., Tanaka, W., Friedman, B.S., Nakashima, M. British journal of clinical pharmacology. (1995) [Pubmed]
  10. 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. Brideau, C., Chan, C., Charleson, S., Denis, D., Evans, J.F., Ford-Hutchinson, A.W., Fortin, R., Gillard, J.W., Guay, J., Guévremont, D. Can. J. Physiol. Pharmacol. (1992) [Pubmed]
  11. Eicosanoids modulate hyperpnea-induced bronchoconstriction in canine peripheral airways. Omori, C., Tagari, P., Freed, A.N. J. Appl. Physiol. (1996) [Pubmed]
  12. Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is not observed in three animal models. Carty, T.J., Sweeney, F.J., Griffiths, R.J., Eskra, J.D., Ernest, M.J., Pillar, J.S., Cheng, J.D., Loose, L.D., Joseph, P.A., Pazoles, P.P., Moore, P.F., Nagahisa, A., Murase, S., Kadin, S.B. Inflamm. Res. (1997) [Pubmed]
  13. Studies of the inhibitory activity of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-indol- 2-yl]-2,2-dimethyl propanoic acid) on arachidonic acid metabolism in human phagocytes. Ménard, L., Laviolette, M., Borgeat, P. Can. J. Physiol. Pharmacol. (1992) [Pubmed]
  14. Regulatory interactions between inducible nitric oxide synthase and eicosanoids in glomerular immune injury. Lianos, E.A., Guglielmi, K., Sharma, M. Kidney Int. (1998) [Pubmed]
  15. Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. Khougaz, K., Clas, S.D. Journal of pharmaceutical sciences. (2000) [Pubmed]
  16. Pharmacokinetic and pharmacodynamic interaction between the lipoxygenase inhibitor MK-0591 and the cyclooxygenase inhibitor ibuprofen in man. Depré, M., Van Hecken, A., Verbesselt, R., De Lepeleire, I., Schwartz, J., Porras, A., Larson, P., Lin, C., De Schepper, P.J. International journal of clinical pharmacology research. (1998) [Pubmed]
  17. Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement. Grenier, S., Flamand, N., Pelletier, J., Naccache, P.H., Borgeat, P., Bourgoin, S.G. J. Leukoc. Biol. (2003) [Pubmed]
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