| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Quiflapon (formerly known as L-686,70 and MK591 free acid) is a novel, potent, selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay. MK-0591 had no effect on rat 5-lipoxygenase. 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. 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. MK-0591 was 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 MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response). These results indicate that MK-0591 is a potent inhibitor of LT biosynthesis both in vitro and in vivo indicating that the compound will be suitable for assessing the role of leukotrienes in pathological situations.
| ln Vitro |
Quiflapon is accessible in whole blood from humans, squirrel monkeys, and rats (IC50 values 510, 69, and 9 nM, respectively), as well as in intact human and induced rat polymorphonuclear leukocytes (PMNL) (IC50 values 3.1 and 6.1 nM, respectively). Rat 5-lipoxygenase is not affected by quilapon. Quiflapon is photoaffinity-tagged to inhibit 5-lipoxygenase-activating protein (FLAP) using two distinct photoaffinity ligands. It exhibits a high affinity for FLAP, with an IC50 value of 1.6 nM in the FLAP binding assay. In human PMNL, 5-lipoxygenase translocation from the cytosol to the membrane can be blocked to prevent 5-lipoxygenase from activating [1].
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| ln Vivo |
Quiflapon has been shown to be a strong inhibitor of LT biosynthesis in vivo in three different settings: an ex vivo challenge in blood drawn from treated rats and squirrel monkeys, a rat pleurisy model, and the inhibition of LTE4 excretion in the urine. Test for allergens in sheep with allergies. Quiflapon was found to have an inhibitory effect on antigen-induced bronchoconstriction (both early and late responses) in ascaris-challenged sheep, ascaris-challenged squirrel monkeys, and inbred rats pretreated with methierg [1]. For days 1-4, 5-9, or 10-14, puppies received daily subcutaneous injections of vehicle or Quiflapon at 10, 20, or 40 mg/kg. Lungs were inflated, fixed, and stained for morphometric and histological studies on day 14. Both the untreated hyperoxia group and the Quiflapon-treated hyperoxia group demonstrated distinct signs of aberrant alveolarization without any inflammation [2].
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| 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. |
| Molecular Formula |
C34H35CLN2O3S
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|---|---|
| Molecular Weight |
587.17100
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| CAS # |
136668-42-3
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| Related CAS # |
Quiflapon sodium;147030-01-1
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| SMILES |
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
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| InChi Key |
NZOONKHCNQFYCI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H35ClN2O3S/c1-33(2,3)41-31-27-18-26(40-21-25-15-12-23-8-6-7-9-28(23)36-25)16-17-29(27)37(20-22-10-13-24(35)14-11-22)30(31)19-34(4,5)32(38)39/h6-18H,19-21H2,1-5H3,(H,38,39)
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| Chemical Name |
3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid
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| Synonyms |
Quiflapon free acid; MK 591; MK-591; MK591; L 686708; L-686708; L686708; L-686,708; L 686,708; L686,708;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~85.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.26 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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