Polypharmacology of Small-Molecule Modulators of the 5-Lipoxygenase Activating Protein (FLAP) Observed via a High-throughput Lipidomics Platform

Journal of Biomolecular Screening

Volumn 21, Issue 2, 2016, Pages 127-135

  Song, Jiao ^a   Liu, Xuejun ^a   Zhu, Jian ^a   Tootoonchi, Mandana ^a   Keith, John M ^a   Meduna, Steven P ^a   Dvorak, Curt A ^a   Eccles, Wendy ^a   Krawczuk, Paul J ^a   Blevitt, Jonathan M ^a   Wu, Jiejun ^a   Rao, Navin L ^a   Lebsack, Alec D ^a   Milla, Marcos E ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

compound differentiation; eicosanoids; FLAP inhibitors; lipidomics; polypharmacology

Indexed keywords

3 [3 TERT BUTYLTHIO 1 (4 CHLOROBENZYL) 5 ISOPROPYL 2 INDOLYL] 2,2 DIMETHYLPROPIONIC ACID; 5 HYDROXYICOSATETRAENOIC ACID; ARACHIDONATE 5 LIPOXYGENASE ACTIVATING PROTEIN; ARACHIDONIC ACID; ICOSANOID; LIPOXIN; PROSTAGLANDIN; QUIFLAPON; THROMBOXANE; ALOX5AP PROTEIN, HUMAN; GLUTATHIONE TRANSFERASE; LEUKOTRIENE; LEUKOTRIENE-C4 SYNTHASE; MOLECULAR LIBRARY;

ARTICLE; BLOOD ANALYSIS; DATA ANALYSIS; DRUG POTENCY; ENZYME ACTIVITY; EX VIVO STUDY; HIGH THROUGHPUT SCREENING; HUMAN; INFORMATION PROCESSING; LIPIDOMICS; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; POLYPHARMACOLOGY; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; CHEMISTRY; MOLECULAR LIBRARY;

5-LIPOXYGENASE-ACTIVATING PROTEINS; EICOSANOIDS; GLUTATHIONE TRANSFERASE; HUMANS; LEUKOTRIENES; POLYPHARMACOLOGY; SMALL MOLECULE LIBRARIES;

EID: 84954526381     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057115607815     Document Type: Article

References (33)

1. Harizi H., Corcuff J. B., Gualde N., Arachidonic-Acid-Derived Eicosanoids: Roles in Biology and Immunopathology. Trends Mol. Med. 2008, 14 (10), 461-469.
2. Murphy R. C., Gijon M. A., Biosynthesis and Metabolism of Leukotrienes. Biochemical J. 2007, 405 (3), 379-395.
3. Greene E. R., Huang S., Serhan C. N., et al. Regulation of Inflammation in Cancer by Eicosanoids. Prostagland. Other Lipid Mediat. 2011, 96 (1-4), 27-36.
4. Miller D. K., Gillard J. W., Vickers P. J., et al. Identification and Isolation of a Membrane Protein Necessary for Leukotriene Production. Nature. 1990, 343 (6255), 278-281.
5. Evans J. F., Ferguson A. D., Mosley R. T., et al. What's All the FLAP About? 5-Lipoxygenase-Activating Protein Inhibitors for Inflammatory Diseases. Trends Pharmacol. Sci. 2008, 29 (2), 72-78.
6. Yokomizo T., Two Distinct Leukotriene B4 Receptors, BLT1 and BLT2. J. Biochemistry. 2015, 157 (2), 65-71.
7. Kaetsu Y., Yamamoto Y., Sugihara S., et al. Role of Cysteinyl Leukotrienes in the Proliferation and the Migration of Murine Vascular Smooth Muscle Cells In Vivo and In Vitro. Cardiovascular Res. 2007, 76 (1), 160-166.
8. Kanaoka Y., Boyce J. A., Cysteinyl Leukotrienes and Their Receptors: Cellular Distribution and Function in Immune and Inflammatory Responses. J. Immunology. 2004, 173 (3), 1503-1510.
9. Powell W. S., Rokach J., The Eosinophil Chemoattractant 5-oxo-ETE and the OXE Receptor. Prog. Lipid Res. 2013, 52 (4), 651-665.
10. Berger W., De Chandt M. T., Cairns C. B., Zileuton: Clinical Implications of 5-Lipoxygenase Inhibition in Severe Airway Disease. Intl. J. Clin. Pract. 2007, 61 (4), 663-676.
11. Awni W. M., Braeckman R. A., Granneman G. R., et al. Pharmacokinetics and Pharmacodynamics of Zileuton after Oral Administration of Single and Multiple Dose Regimens of Zileuton 600 mg in Healthy Volunteers. Clin. Pharmacol. 1995, 29 (Suppl. 2), 22-33.
12. Xu J. J., Henstock P. V., Dunn M. C., et al. Cellular Imaging Predictions of Clinical Drug-Induced Liver Injury. Toxicological Sci. 2008, 105 (1), 97-105.
13. Sampson A. P., FLAP Inhibitors for the Treatment of Inflammatory Diseases. Curr. Opin. Investigational Drugs. 2009, 10 (11), 1163-1172.
14. Byrum R. S., Goulet J. L., Griffiths R. J., et al. Role of the 5-Lipoxygenase-Activating Protein (FLAP) in Murine Acute Inflammatory Responses. J. Experimental Med. 1997, 185 (6), 1065-1075.
15. Helgadottir A., Manolescu A., Thorleifsson G., et al. The Gene Encoding 5-Lipoxygenase Activating Protein Confers Risk of Myocardial Infarction and Stroke. Nature Genet. 2004, 36 (3), 233-239.
16. Wang D., Dubois R. N., Eicosanoids and Cancer. Nature Rev. Cancer. 2010, 10 (3), 181-193.
17. Ferguson A. D., McKeever B. M., Xu S., et al. Crystal Structure of Inhibitor-Bound Human 5-Lipoxygenase-Activating Protein. Science. 2007, 317 (5837), 510-512.
18. Hopkins A. L., Drug Discovery: Predicting Promiscuity. Nature. 2009, 462 (7270), 167-168.
19. Song J., Liu X., Wu J., et al. A Highly Efficient, High-Throughput Lipidomics Platform for the Quantitative Detection of Eicosanoids in Human Whole Blood. Analytical Biochem. 2013, 433 (2), 181-188.
20. Bain G., King C. D., Rewolinski M., et al. Pharmacodynamics and Pharmacokinetics of AM103, a Novel Inhibitor of 5-Lipoxygenase-Activating Protein (FLAP). Clin. Pharmacol. Therapeutics. 2010, 87 (4), 437-444.
21. Dumlao D. S., Buczynski M. W., Norris P. C., et al. High-Throughput Lipidomic Analysis of Fatty Acid Derived Eicosanoids and N-Acylethanolamines. Biochim. Biophys. Acta. 2011, 1811 (11), 724-736.
22. Yamada M., Kita Y., Kohira T., et al. A Comprehensive Quantification Method for Eicosanoids and Related Compounds by Using Liquid Chromatography/Mass Spectrometry with High Speed Continuous Ionization Polarity Switching. J. Chromatography B. 2015, 995-996, 74-84.
23. Murphy R. C., Barkley R. M., Zemski Berry K., et al. Electrospray Ionization and Tandem Mass Spectrometry of Eicosanoids. Analytical Biochem. 2005, 346 (1), 1-42.
24. Mesaros C., Lee S. H., Blair I. A., Targeted Quantitative Analysis of Eicosanoid Lipids in Biological Samples Using Liquid Chromatography-Tandem Mass Spectrometry. J. Chromatography B. 2009, 877 (26), 2736-2745.
25. Klawitter J., Zafar I., Klawitter J., et al. Effects of Lovastatin Treatment on the Metabolic Distributions in the Han:SPRD Rat Model of Polycystic Kidney Disease. BMC Nephrol. 2013, 14, 165.
26. Grant G. E., Rokach J., Powell W. S., 5-Oxo-ETE and the OXE Receptor. Prostagland. Other Lipid Mediat. 2009, 89 (3-4), 98-104.
27. Zamaria N., Alteration of Polyunsaturated Fatty Acid Status and Metabolism in Health and Disease. Reproduction Nutr. Devel. 2004, 44 (3), 273-282.
28. Roth B. L., Sheffler D. J., Kroeze W. K., Magic Shotguns versus Magic Bullets: Selectively Non-selective Drugs for Mood Disorders and Schizophrenia. Nature Rev. Drug Discov. 2004, 3 (4), 353-359.
29. Powell W. S., Chung D., Gravel S., 5-Oxo-6,8,11,14-Eicosatetraenoic Acid Is a Potent Stimulator of Human Eosinophil Migration. J. Immunol. 1995, 154 (8), 4123-4132.
30. Song J., Liu X., Rao T. S., et al. Phenotyping Drug Polypharmacology via Eicosanoid Profiling of Blood. J. Lipid Res. 2015, 56 (8): 1492-1500.
31. Singh D., Boyce M., Norris V., et al. Inhibition of the Early Asthmatic Response to Inhaled Allergen by the 5-Lipoxygenase Activating Protein Inhibitor GSK2190915: A Dose-Response Study. Intl. J. Gen. Med. 2013, 6, 897-903.
32. Brideau C., Chan C., Charleson S., 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. Canad. J. Physiol. Pharmacol. 1992, 70 (6), 799-807.
33. Lorrain D. S., Bain G., Correa L. D., et al. 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. Exper. Therapeut. 2009, 331 (3), 1042-1050.