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Quiflapon

CAS No. : 136668-42-3

MCE 国际站：Quiflapon

产品活性：Quiflapon (MK-591)是一种选择性和特异性的 FLAP 抑制剂，IC₅₀ 为 1.6 nM。Quiflapon 也是一种有效的口服白三烯生物合成 (leukotriene biosynthesis) 抑制剂，在完整的人和诱导的大鼠多形核白细胞 PMNLs 中，其 IC₅₀ 值分别为 3.1 nM 和 6.1 nM。Quiflapon 可以诱导细胞凋亡 (apoptosis)。

研究领域：Immunology/Inflammation  |  Apoptosis

作用靶点：FLAP  |  Apoptosis

In Vitro: 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.

In Vivo: 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) [1]. 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.

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