Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1

Journal of Pharmacology and Experimental Therapeutics

Volumn 326, Issue 3, 2008, Pages 975-982

  Koeberle, Andreas ^a   Siemoneit, Ulf ^a   Bühring, Ulrike ^a   Northoff, Hinnak ^b   Laufer, Stefan ^a   Albrecht, Wolfgang ^a   Werz, Oliver ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

3 [3 TERT BUTYLTHIO 1 (4 CHLOROBENZYL) 5 ISOPROPYL 2 INDOLYL] 2,2 DIMETHYLPROPIONIC ACID; ARACHIDONATE 5 LIPOXYGENASE; ARACHIDONIC ACID; CALCIMYCIN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; INTERLEUKIN 1BETA; LICOFELONE; PROSTAGLANDIN E2; PROSTAGLANDIN F1 ALPHA; PROSTAGLANDIN SYNTHASE; ISOMERASE; PROSTAGLANDIN E SYNTHASE; PYRROLE DERIVATIVE;

ARTICLE; CELL CULTURE; CELL VIABILITY; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INDUCTION; HUMAN; HUMAN CELL; IC 50; OSTEOARTHRITIS; PRIORITY JOURNAL; PROSTAGLANDIN SYNTHESIS INHIBITION; THROMBOCYTE; ADULT; ANIMAL; BIOSYNTHESIS; CATTLE; COMPARATIVE STUDY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; METABOLISM; MICROSOME; SHEEP;

ADULT; ANIMALS; CATTLE; CELLS, CULTURED; DINOPROSTONE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INTRAMOLECULAR OXIDOREDUCTASES; MICROSOMES; PYRROLES; SHEEP;

EID: 52649119793     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.139444     Document Type: Article

References (40)

1. Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, and Werz O (2002) Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol 64:1767-1775.
2. Asano K, Lilly CM, and Drazen JM (1996) Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 271:L126-L131.
3. Bias P, Buchner A, Klesser B, and Laufer S (2004) The gastrointestinal tolerability of the LOX/COX inhibitor, licofelone, is similar to placebo and superior to naproxen therapy in healthy volunteers: results from a randomized, controlled trial. Am J Gastroenterol 99:611-618.
4. Capdevila JH, Morrow JD, Belosludtsev YY, Beauchamp DR, DuBois RN, and Falck JR (1995) The catalytic outcomes of the constitutive and the mitogen inducible isoforms of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase(s). Biochemistry 34:3325-3337.
5. Celotti F and Laufer S (2001) Anti-inflammatory drugs: new multitarget compounds to face an old problem. The dual inhibition concept. Pharmacol Res 43:429-436.
6. Cheng Y, Wang M, Yu Y, Lawson J, Funk CD, and Fitzgerald GA (2006) Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 116:1391-1399.
7. Claveau D, Sirinyan M, Guay J, Gordon R, Chan CC, Bureau Y, Riendeau D, and Mancini JA (2003) Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis model. J Immunol 170:4738-4744.
8. Côté B, Boulet L, Brideau C, Claveau D, Ethier D, Frenette R, Gagnon M, Giroux A, Guay J, Guiral S, et al. (2007) Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors. Bioorg Med Chem Lett 17:6816-6820.
9. Fischer L, Hornig M, Pergola C, Meindl N, Franke L, Tanrikulu Y, Dodt G, Schneider G, Steinhilber D, and Werz O (2007) The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5-lipoxygenase products. Br J Pharmacol 152:471-480.
10. Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294:1871-1875.
11. Gillard J, Ford-Hutchinson AW, Chan C, Charleson S, Denis D, Foster A, Fortin R, Leger S, McFarlane CS, Morton H, et al. (1989) L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2, 2-dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol 67:456-464.
12. Hawkey CJ (1999) COX-2 inhibitors. Lancet 353:307-314.
13. Jachak SM (2007) PGE synthase inhibitors as an alternative to COX-2 inhibitors. Curr Opin Investig Drugs 8:411-415.
14. Jakobsson PJ, Thorén S, Morgenstern R, and Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96:7220-7225.
15. Jovanovic DV, Fernandes JC, Martel-Pelletier J, Jolicoeur FC, Reboul P, Laufer S, Tries S, and Pelletier JP (2001) In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: suppression of collagenase 1 and interleukin-1beta synthesis. Arthritis Rheum 44:2320-2330.
16. Kato K, Ohkawa S, Terao S, Terashita Z, and Nishikawa K (1985) Thromboxane synthetase inhibitors (TXSI). Design, synthesis, and evaluation of a novel series of omega-pyridylalkenoic acids. J Med Chem 28:287-294.
17. Kulkarni SK and Singh VP (2007) Licofelone - a novel analgesic and anti-inflammatory agent. Curr Top Med Chem 7:251-263.
18. Lajeunesse D, Martel-Pelletier J, Fernandes JC, Laufer S, and Pelletier JP (2004) Treatment with licofelone prevents abnormal subchondral bone cell metabolism in experimental dog osteoarthritis. Ann Rheum Dis 63:78-83.
19. Laufer S, Tries S, Augustin J, and Dannhardt G (1994a) Pharmacological profile of a new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase. Arzneimittelforschung 44:629-636.
20. Laufer SA, Augustin J, Dannhardt G, and Kiefer W (1994b) (6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase. J Med Chem 37:1894-1897.
21. McGettigan P and Henry D (2006) Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 296:1633-1644.
22. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, and Vane JR (1993) Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A 90:11693-11697.
23. Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y, Kojima F, Ikeda T, Fueki M, Ueno A, Oh S, et al. (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783- 32792.
24. Paredes Y, Massicotte F, Pelletier JP, Martel-Pelletier J, Laufer S, and Lajeunesse D (2002) Study of the role of leukotriene B(4) in abnormal function of human subchondral osteoarthritis osteoblasts: effects of cyclooxygenase and/or 5-lipoxygenase inhibition. Arthritis Rheum 46:1804-1812.
25. Park JY, Pillinger MH, and Abramson SB (2006) Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol 119:229-240.
26. Peters-Golden M and Henderson WR Jr (2007) Leukotrienes. N Engl J Med 357:1841-1854.
27. Rainsford KD (2007) Anti-inflammatory drugs in the 21st century. Subcell Biochem 42:3-27.
28. Riendeau D, Aspiotis R, Ethier D, Gareau Y, Grimm EL, Guay J, Guiral S, Juteau H, Mancini JA, Méthot N, et al. (2005) Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886. Bioorg Med Chem Lett 15:3352-3355.
29. Rotondo S, Dell'Elba G, Manarini S, Cerletti C, and Evangelista V (2006) The lipoxygenase-cyclooxygenase inhibitor licofelone prevents thromboxane A2-mediated cardiovascular derangement triggered by the inflammatory peptide fMLP in the rabbit. Eur J Pharmacol 546:95-101.
30. Samuelsson B, Morgenstern R, and Jakobsson PJ (2007) Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 59:207-224.
31. Smith WL (1989) The eicosanoids and their biochemical mechanisms of action. Biochem J 259:315-324.
32. Thorén S and Jakobsson PJ (2000) Coordinate up- and down-regulation of glutathione-dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells. Inhibition by NS-398 and leukotriene C4. Eur J Biochem 267:6428-6434.
33. Trebino CE, Stock JL, Gibbons CP, Naiman BM, Wachtmann TS, Umland JP, Pandher K, Lapointe JM, Saha S, Roach ML, et al. (2003) Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase. Proc Natl Acad Sci U S A 100:9044-9049.
34. Tries S, Laufer S, Radziwon P, and Breddin HK (2002a) Antithrombotic and platelet function inhibiting effects of ML3000, a new antiinflammatory drug with Cox/5-LOX inhibitory activity. Inflamm Res 51:129-134.
35. Tries S, Neupert W, and Laufer S (2002b) The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2. Inflamm Res 51:135-143.
36. Vidal C, Gómez-Hernández A, Sánchez-Galan E, González A, Ortega L, Gómez-Gerique JA, Tuñón J, and Egido J (2007) Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. J Pharmacol Exp Ther 320:108-116.
37. Wallace JL, Carter L, McKnight W, Tries S, and Laufer S (1994) ML 3000 reduces gastric prostaglandin synthesis without causing mucosal injury. Eur J Pharmacol 271:525-531.
38. Wang M, Zukas AM, Hui Y, Ricciotti E, Puré E, and FitzGerald GA (2006) Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis. Proc Natl Acad Sci U S A 103:14507- 14512.
39. Warner TD, Vojnovic I, Bishop-Bailey D, and Mitchell JA (2006) Influence of plasma protein on the potencies of inhibitors of cyclooxygenase-1 and -2. FASEB J 20:542-544.
40. Yamamoto S, Yokota K, Tonai T, Shono F, and Hayashi Y (1987) Enzyme immunoassay, in Prostaglandins and Related Substances - A Practical Approach (Benedetto C, McDonald-Gibson RG, Nigam S, and Slater TF eds) pp 197-208, IRL Press, Washington, DC.