Quiflapon | MK 0591 | CAS#136668-42-3 | 147030-01-1 | FLAP inhibitor

Quiflapon sodium
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 326735

CAS#: 147030-01-1 (sodium)

Description: Quiflapon, also known as MK 0591, is a potent and selective 5-Lipoxygenase-activating protein (FLAP) inhibitor. MK-0591 is also 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). 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.

Chemical Structure

Quiflapon sodium

CAS# 147030-01-1 (sodium)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 326735
Name: Quiflapon sodium
CAS#: 147030-01-1 (sodium)
Chemical Formula: C34H34ClN2NaO3S
Exact Mass: 608.19
Molecular Weight: 609.157
Elemental Analysis: C, 67.04; H, 5.63; Cl, 5.82; N, 4.60; Na, 3.77; O, 7.88; S, 5.26

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 390
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Related CAS #: 136668-42-3 (free base) 147030-01-1 (sodium)

Synonym: MK 0591; MK-0591; MK0591; L 686708; L-686708; L686708; L-686,708; L 686,708; L686,708; MK 591; MK591; MK-591; Quiflapon; Quiflapon sodium;

IUPAC/Chemical Name: sodium 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate

InChi Key: YPURUCMVRRNPHJ-UHFFFAOYSA-M

InChi Code: InChI=1S/C34H35ClN2O3S.Na/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);/q;+1/p-1

SMILES Code: O=C(C(C)(CC(N1CC2=CC=C(C=C2)Cl)=C(C3=C1C=CC(OCC4=NC5=CC=CC=C5C=C4)=C3)SC(C)(C)C)C)O[Na]

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	Quiflapon sodium is a potent and selective 5-Lipoxygenase-activating protein (FLAP) inhibitor. MK-0591 is also 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). 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.
In vitro activity:	Experiments with the 5-LO-activating protein inhibitor MK-0591 and the intracellular Ca2+ chelator BAPTA-AM demonstrated that the arachidonic acid (AA)-regulated 5-LO translocation is FLAP- and Ca2+-dependent. The redox and competitive 5-lipoxygenase inhibitors L-685,015, L-739,010, and L-702,539 efficiently substituted for AA to reverse the pyrrophenone inhibition of 5-LO translocation, indicating that the site of regulation of 5-LO translocation by AA is at or in the vicinity of the catalytic site. This report demonstrates that AA regulates the translocation of 5-LO in human PMN and unravels a novel mechanism of the cAMP-mediated inhibition of LT biosynthesis. Reference: J Biol Chem. 2006 Jan 6;281(1):129-36. https://pubmed.ncbi.nlm.nih.gov/16275640/
In vivo activity:	Mice with either genetic (5-LO(-/-)) or pharmacological (MK-0591) inhibition of the 5-LO pathway on an apolipoprotein E-deficient (apoE(-/-)). Ang II-induced marked aortic wall remodeling with an incidence of 32, 29 and 40% AAA formation in 5-LO(-/-) apoE(-/-), 5-LO(+/+)apoE(-/-) and 5-LO(+/+)apoE(-/-) mice treated with FLAP inhibitor MK-0591, respectively, with no statistically significant differences in incidence or severity between groups. Abrogation of the 5-LO pathway in mice indicates a lack of role of leukotrienes in Ang II-induced AAA pathogenesis stressing the need for additional non-rodent AAA pre-clinical models to be tested. Reference: Prostaglandins Other Lipid Mediat. 2007 Aug;84(1-2):34-42. https://pubmed.ncbi.nlm.nih.gov/17643886/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	50.0	82.08

Preparing Stock Solutions

The following data is based on the product molecular weight 609.16 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	Marleau S, Fruteau de Laclos B, Sanchez AB, Poubelle PE, Borgeat P. Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit. J Immunol. 1999 Sep 15;163(6):3449-58. PMID: 10477617.
In vitro protocol:	1. Flamand N, Lefebvre J, Surette ME, Picard S, Borgeat P. Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J Biol Chem. 2006 Jan 6;281(1):129-36. doi: 10.1074/jbc.M506513200. Epub 2005 Nov 7. PMID: 16275640. 2. Surette ME, Krump E, Picard S, Borgeat P. Activation of leukotriene synthesis in human neutrophils by exogenous arachidonic acid: inhibition by adenosine A(2a) receptor agonists and crucial role of autocrine activation by leukotriene B(4). Mol Pharmacol. 1999 Nov;56(5):1055-62. doi: 10.1124/mol.56.5.1055. PMID: 10531413.
In vivo protocol:	1. Cao RY, Adams MA, Habenicht AJ, Funk CD. Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice. Prostaglandins Other Lipid Mediat. 2007 Aug;84(1-2):34-42. doi: 10.1016/j.prostaglandins.2007.03.005. Epub 2007 Mar 24. PMID: 17643886. 2. Marleau S, Fruteau de Laclos B, Sanchez AB, Poubelle PE, Borgeat P. Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit. J Immunol. 1999 Sep 15;163(6):3449-58. PMID: 10477617.

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1: Park MS, Sohn MH, Kim KE, Park MS, Namgung R, Lee C. 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. doi: 10.1007/s00408-010-9264-1. Epub 2010 Nov 5. PubMed PMID: 21052705.

2: Khougaz K, Clas SD. Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. J Pharm Sci. 2000 Oct;89(10):1325-34. PubMed PMID: 10980507.

3: Depré M, Van Hecken A, Verbesselt R, De Lepeleire I, Schwartz J, Porras A, Larson P, Lin C, De Schepper PJ. Pharmacokinetic and pharmacodynamic interaction

between the lipoxygenase inhibitor MK-0591 and the cyclooxygenase inhibitor ibuprofen in man. Int J Clin Pharmacol Res. 1998;18(2):53-61. PubMed PMID: 9675622.

4: Uematsu T, Kanamaru M, Kosuge K, Hara K, Uchiyama N, Takenaga N, Tanaka W, Friedman BS, Nakashima M. Pharmacokinetic and pharmacodynamic analysis of a novel leukotriene biosynthesis inhibitor, MK-0591, in healthy volunteers. Br J Clin Pharmacol. 1995 Jul;40(1):59-66. PubMed PMID: 8527269; PubMed Central PMCID: PMC1365028.

5: Hillingsø J, Kjeldsen J, Laursen LS, Lauritsen K, von Spreckelsen S, Depré M,

Friedman BS, Malmström K, Shingo S, Bukhave K, et al. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis. Clin Pharmacol Ther. 1995 Mar;57(3):335-41. PubMed PMID: 7697951.

6: Becker AB, Black C, Lilley MK, Bajwa K, Ford-Hutchinson AW, Simons FE, Tagari

P. Antiasthmatic effects of a leukotriene biosynthesis inhibitor (MK-0591) in allergic dogs. J Appl Physiol (1985). 1995 Feb;78(2):615-22. PubMed PMID: 7759431.

7: Diamant Z, Timmers MC, van der Veen H, Friedman BS, De Smet M, Depré M, Hilliard D, Bel EH, Sterk PJ. 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. J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):42-51. PubMed PMID: 7822663.

8: Depré M, Friedman B, Van Hecken A, de Lepeleire I, Tanaka W, Dallob A, Shingo

S, Porras A, Lin C, de Schepper PJ. Pharmacokinetics and pharmacodynamics of multiple oral doses of MK-0591, a 5-lipoxygenase-activating protein inhibitor. Clin Pharmacol Ther. 1994 Jul;56(1):22-30. PubMed PMID: 8033491.

9: Stevens WH, Lane CG, Woolley MJ, Ellis R, Tagari P, Black C, Ford-Hutchinson A, O'Byrne PM. Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs. J Appl Physiol (1985). 1994 Apr;76(4):1583-8. PubMed PMID: 8045835.

10: Tagari P, Becker A, Brideau C, Frenette R, Sadl V, Thomas E, Vickers P, Ford-Hutchinson A. Leukotriene generation and metabolism in dogs: inhibition of biosynthesis by MK-0591. J Pharmacol Exp Ther. 1993 Apr;265(1):416-25. PubMed PMID: 8386242.

11: Prasit P, Belley M, Blouin M, Brideau C, Chan C, Charleson S, Evans JF, Frenette R, Gauthier JY, Guay J, et al. A new class of leukotriene biosynthesis inhibitor: the development of MK-0591. J Lipid Mediat. 1993 Mar-Apr;6(1-3):239-44. PubMed PMID: 8357985.

12: Ménard L, Laviolette M, Borgeat P. 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. Can J Physiol Pharmacol. 1992 Jun;70(6):808-13. PubMed PMID: 1423024.

13: Brideau C, Chan C, Charleson S, Denis D, Evans JF, Ford-Hutchinson AW, Fortin R, Gillard JW, Guay J, Guévremont D, 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):799-807. PubMed PMID: 1330258.

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Quiflapon sodium featured