Pharmacology of PF-4191834, a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain

Journal of Pharmacology and Experimental Therapeutics

Volumn 334, Issue 1, 2010, Pages 294-301

  Masferrer, Jaime L ^a   Zweifel, Ben S ^a   Hardy, Medora ^a   Anderson, Gary D ^a   Dufield, Dawn ^a   Cortes Burgos, Luz ^a   Pufahl, Robert A ^a   Graneto, Matthew ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIPOXYGENASE INHIBITOR; PF 4191834; PROSTAGLANDIN SYNTHASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD CELL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME ASSAY; IC 50; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MALE; NONHUMAN; PAIN; PRIORITY JOURNAL; RAT;

ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; ASTHMA; CHROMATOGRAPHY, LIQUID; DISEASE MODELS, ANIMAL; HUMANS; INFLAMMATION; LEUKOCYTES; LEUKOTRIENE B4; LIPOXYGENASE INHIBITORS; MALE; MASS SPECTROMETRY; OXIDATION-REDUCTION; PAIN; PYRAZOLES; RATS; RATS, INBRED LEW; RATS, SPRAGUE-DAWLEY; SPECTROPHOTOMETRY; SULFIDES;

EID: 77953771000     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.166967     Document Type: Article

References (37)

1. Abraham WM, Ahmed A, Cortes A, Sielczak MW, Hinz W, Bouska J, Lanni C, and Bell RL (1992) The 5-lipoxygenase inhibitor zileuton blocks antigen-induced late airway responses, inflammation and airway hyperresponsiveness in allergic sheep. Eur J Pharmacol 217:119-126.
2. Awni WM, Braeckman RA, Granneman GR, Witt G, and Dubé LM (1995) Pharmacokinetics and pharmacodynamics of zileuton after oral administration of single and multiple dose regimens of zileuton 600 mg in healthy volunteers. Clin Pharmacokinet 29 (Suppl 2):22-33.
3. Camargo CA Jr, Smithline HA, Malice MP, Green SA, and Reiss TF (2003) A randomized controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med 167:528-533.
4. Cortes-Burgos LA, Zweifel BS, Settle SL, Pufahl RA, Anderson GD, Hardy MM, Weir DE, Hu G, Happa FA, Stewart Z, et al. (2009) CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain. Eur J Pharmacol 617:59-67.
5. Diamant Z, Timmers MC, van der Veen H, Friedman BS, De Smet M, Depré M, Hilliard D, Bel EH, and Sterk PJ (1995) The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergeninduced airway responses in asthmatic subjects in vivo. J Allergy Clin Immunol 95:42-51.
6. Drazen J (1998) Clinical pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Am J Respir Crit Care Med 157:S233-S237. (Pubitemid 28304149)
7. Evans JF, Ferguson AD, Mosley RT, and Hutchinson JH (2008) What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci 29:72-78.
8. Falgueyret JP, Hutchinson JH, and Riendeau D (1993) Criteria for the identification of non-redox inhibitors of 5-lipoxygenase. Biochem Pharmacol 45:978-981.
9. Fischer L, Steinhilber D, and Werz O (2004) Molecular pharmacological profile of the nonredox-type 5-lipoxygenase inhibitor CJ-13,610. Br J Pharmacol 142:861-868.
10. Friedman BS, Bel EH, Buntinx A, Tanaka W, Han YH, Shingo S, Spector R, and Sterk P (1993) Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses. Am Rev Resp Dis 147:839-844.
11. Guilbert M, Ferland C, Bossé M, Flamand N, Lavigne S, and Laviolette M (1999) 5-Oxo-6,8,11,14-eicosatetraenoic acid induces important eosinophil transmigration through basement membrane components: comparison of normal and asthmatic eosinophils. Am J Respir Cell Mol Biol 21:97-104.
12. Hackshaw KV, Voelkel NF, Thomas RB, and Westcott JY (1992) Urine leukotriene E4 levels are elevated in patients with active systemic lupus erythematosus. J Rheumatol 19:252-258.
13. Hackshaw KV, Shi Y, Brandwein SR, Jones K, and Westcott JY (1995) A pilot study of zileuton, a novel selective 5-lipoxygenase inhibitor, in patients with systemic lupus erythematosus. J Rheumatol 22:462-468.
14. Harris RR, Carter GW, Bell RL, Moore JL, and Brooks DW (1995) Clinical activity of leukotriene inhibitors. Int J Immunopharmacol 17:147-156.
15. Hui KP, Taylor IK, Taylor GW, Rubin P, Kesterson J, Barnes NC, and Barnes PJ (1991) Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients. Thorax 46:184-189.
16. Stechschulte DJ (1990) Leukotrienes in asthma and allergic rhinitis.N Engl J Med 323:1769-1770.
17. Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, Tinkelman D, Murray JJ, Busse W, Segal AT, et al. (1993) The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 119:1059-1066.
18. Joshi EM, Heasley BH, Chordia MD, and Macdonald TL (2004) In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity. Chem Res Toxicol 17:137-143.
19. Kanai A, Mori S, Osawa S, Suzuki A, and Hoka S (2004) Efficacy of oral pranlukast hydrate, a leukotriene receptor antagonist, in the treatment of postherpetic neuralgia. Pain Clinic 16:389-392.
20. Kremer JM and Brandwein SR (1994) Effect of zileuton, a novel selective 5-lipoxygenase inhibitor in rheumatoid arthritis. Arthritis Rheum 37 (Suppl): 341.
21. Liu MC, Dubé LM, and Lancaster J (1996) Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. J Allergy Clin Immunol 98:859-871.
22. Lorrain DS, Bain G, Correa LD, Chapman C, Broadhead AR, Santini AM, Prodanovich P, Darlington JV, Hutchinson JH, King C, et al. (2009) Pharmacological characterization of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy- pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid (AM103), a novel selective 5-lipoxygenase-activating protein inhibitor that reduces acute and chronic inflammation. J Pharmacol Exp Ther 331:1042-1050.
23. Mano T, Stevens RW, Ando K, Kawai M, Kawamura K, Nakao K, Okumura Y, Okumura T, Sakakibara M, Miyamoto K, et al. (2005) Optimization of imidazole 5-lipoxygenase inhibitors and selection and synthesis of a development candidate. Chem Pharm Bull 53:965-973.
24. Miller TA, Ghosh J, Myers CE, and Macdonald TL (2000) 5-HETE congeners as modulators of cell proliferation. Bioorg Med Chem Lett 10:1913-1916.
25. Mitsunobu F, Mifune T, Hosaki Y, Ashida K, Tsugeno H, Okamoto M, Harada S, Takata S, Tanizaki Y, and Harada M (2000) Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics. Eur Respir J16:504-508.
26. Muro S, Hamid Q, Olivenstein R, Taha R, Rokach J, and Powell WS (2003) 5-oxo-6,8,11,14-Eicosatetraenoic acid induces the infiltration of granulocytes into human skin. J Allergy Clin Immunol 112:768-774.
27. Peters-Golden M and Henderson WR Jr (2007) Leukotrienes. N Engl J Med 357:1841-1854.
28. Powell WS and Rokach J (2005) Biochemistry, biology and chemistry of the 5-lipoxygenase product 5-oxo-ETE. Prog Lipid Res 44:154-183.
29. Pufahl RA, Kasten TP, Hills R, Gierse JK, Reitz BA, Weinberg RA, and Masferrer JL (2007) Development of a fluorescence-based enzyme assay of human 5-lipoxygenase. Anal Biochem 364:204-212.
30. Randall LO and Selitto JJ (1957) A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther 111:409-419.
31. Rastogi P and McHowat J (2006) Eicosanoids as therapeutic targets in asthma. Lett Drug Design Discov 3:668-674.
32. Rubin P and Mollison KW (2007) Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Prostaglandins Other Lipid Mediat 83:188-197.
33. Samuelsson B (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 4819:1171-1176.
34. Stamatiou P, Hamid Q, Taha R, Yu W, Issekutz TB, Rokach J, Khanapure SP, and Powell WS (1998) 5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats. J Clin Invest 102:2165-2172.
35. Tagari P, Brideau C, Chan C, Frenette R, Black C, and Ford-Hutchinson A (1993) Assessment of the in vivo biochemical efficacy of orally active leukotriene biosynthesis inhibitors. Agents Actions 40:62-71.
36. Young R (1999) Inhibitors of 5-lipoxygenase: a therapeutic potential yet to be fully realized? Eur J Med Chem 34:671-685.
37. Zweifel BS, Hardy MM, Anderson GD, Dufield DR, Pufahl RA, and Masferrer JL (2008) A rat air pouch model for evaluating the efficacy and selectivity of 5-lipoxygenase inhibitors. Eur J Pharmacol 584:166-174.