[CAS NO. 136668-42-3] Quiflapon
PRODUCTS SPECIFICATIONS [136668-42-3]
DESCRIPTION [136668-42-3]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 587.17 |
| Molecular Formula | C34H35ClN2O3S |
| SMILES | O=C(O)C(C)(C)CC1=C(SC(C)(C)C)C2=C(C=CC(OCC3=NC4=CC=CC=C4C=C3)=C2)N1CC5=CC=C(Cl)C=C5 |
Summary
Quiflapon (MK-591) is a selective and specific 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC 50 of 1.6 nM in a FLAP binding assay. Quiflapon is also a potent and orally active Leukotriene biosynthesis (LT) inhibitor, shows IC 50 values of 3.1 and 6.1 nM in intact human and elicited rat PMNLs, respectively. Quiflapon induces cell apoptosis [1] [2] .
IC50 & Target
IC50: 1.6 nM (FLAP) [1] .
In Vitro
Quiflapon is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC 50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC 50 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 IC 50 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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 85.15 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.7031 mL | 8.5154 mL | 17.0308 mL |
| 5 mM | 0.3406 mL | 1.7031 mL | 3.4062 mL |
| 10 mM | 0.1703 mL | 0.8515 mL | 1.7031 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.26 mM); Clear solution
References
- [1] Brideau C, 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 Jun;70(6):799-8
- [2] Park MS, et al. 5-Lipoxygenase-activating protein (FLAP) inhibitor MK-0591 prevents aberrant alveolarization in newborn mice exposed to 85% oxygen in a dose- and time-dependent manner. Lung. 2011 Feb;189(1):43-50.