MK-0591

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效、特异性、口服活性的 5-脂氧合酶激活蛋白 (FLAP) 抑制剂，在 FLAP 结合测定中 IC50 为 1.6 nM。

A potent, specific and orally active 5-Lipoxygenase-activating protein (FLAP) inhibitor with IC50 of 1.6 nM in FLAP binding assay; has no inhibitory effect on 15-lipoxygenase and platelet 12-lipoxygenase and cyclooxygenase in human PMNLs; potently inhibits leukotriene (LT) biosynthesis in intact human and elicited rat PMNLs with IC50 of 3.1 and 6.1 nM, respectively; inhibits excretion of LTE4 in antigen-challenged allergic animal models.Asthma Discontinued.

Quiflapon is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). Quiflapon has no effect on rat 5-lipoxygenase. Quiflapon 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. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs.

Quiflapon is a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by Quiflapon is observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response) . Pups were treated with either vehicle or Quiflapon 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with Quiflapon untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation.

Quiflapon | MK-591 | L-686708

Immunology/Inflammation

FLAP

FLAP

Inflammation/Immunology

Asthma

136668-42-3

587.1713

C34H35ClN2O3S

>98% (HPLC)

10 mM in DMSO

O=C(O)C(C)(C)CC(N1CC2=CC=C(Cl)C=C2)=C(SC(C)(C)C)C3=C1C=CC(OCC4=NC5=CC=CC=C5C=C4)=C3

1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-α,α-dimethyl-5-(2-quinolinylmethoxy)-

(-20℃)

With Ice Pack

≥ 2 years