Screening and characterization of human monoglyceride lipase active site inhibitors using orthogonal binding and functional assays

Journal of Biomolecular Screening

Volumn 17, Issue 5, 2012, Pages 629-640

  Clemente, José C ^a,b   Nulton, Erica ^b   Nelen, Marina ^b   Todd, Matthew J ^b   Maguire, Diane ^c   Schalk Hihi, Céline ^c   Kuo, Lawrence C ^c   Zhang, Sui Po ^c   Flores, Christopher M ^c   Kranz, James K ^a,b  

^a GLAXOSMITHKLINE   (United States)

^b Lead Generation Biology Janssen Research Asnd Development LLC   (United States)

^c JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

2 arachidonylglycerol; endocannabinoids; high throughput screening; monoglyceride lipase; ThermoFluor

Indexed keywords

2 ARACHIDONOYLGLYCEROL; 4 METHYLCOUMARIN BUTYRATE; ACYLGLYCEROL LIPASE; CANNABINOID RECEPTOR; COUMARIN DERIVATIVE; ENDOCANNABINOID; ENZYME INHIBITOR; MONOGLYCERIDE LIPASE ACTIVE SITE INHIBITOR; UNCLASSIFIED DRUG;

ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; BINDING ASSAY; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; ENZYME SUBSTRATE; FLUORESCENCE; HIGH THROUGHPUT SCREENING; HUMAN; IC 50; LIGAND BINDING; PAIN; PRIORITY JOURNAL; PROTEIN STABILITY; SCREENING TEST; SIGNAL TRANSDUCTION; THERMOSTABILITY;

ARACHIDONIC ACIDS; CATALYTIC DOMAIN; ENZYME ASSAYS; ENZYME INHIBITORS; GLYCERIDES; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; HYDROLYSIS; INHIBITORY CONCENTRATION 50; KINETICS; MONOACYLGLYCEROL LIPASES; PROTEIN BINDING; SOLUBILITY; SUBSTRATE SPECIFICITY;

EID: 84861795634     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057112441012     Document Type: Article

References (26)

1. Hohmann A. G.. Spinal and Peripheral Mechanisms of Cannabinoid Antinociception: Behavioral, Neurophysiological and Neuroanatomical Perspectives. Chem. Phys. Lipids. 2002 ; 121 (1-2). 173-190
2. Malan T. P., Ibrahim M. M., Vanderah T. W., Makriyannis A., Porreca F.. Inhibition of Pain Responses by Activation of CB(2) Cannabinoid Receptors. Chem. Phys. Lipids. 2002 ; 121 (1-2). 191-200
3. Bloom A. S., Dewey W. L., Harris L. S., Brosius K. K.. 9-Nor-9beta-hydroxyhexahydrocannabinol, a Cannabinoid with Potent Antinociceptive Activity: Comparisons with Morphine. J. Pharmacol. Exp. Ther. 1977 ; 200 (2). 263-270
4. Guindon J., Desroches J., Beaulieu P.. The Antinociceptive Effects of Intraplantar Injections of 2-Arachidonoyl Glycerol Are Mediated by Cannabinoid CB2 Receptors. Br. J. Pharmacol. 2007 ; 150 (6). 693-701
5. Kosersky D. S., Dewey W. L., Harris L. S.. Antipyretic, Analgesic and Anti-Inflammatory Effects of Delta 9-Tetrahydrocannabinol in the Rat. Eur. J. Pharmacol. 1973 ; 24 (1). 1-7
6. Mechoulam R., Ben-Shabat S., Hanus L., Ligumsky M., Kaminski N. E., Schatz A. R., Gopher A., Almog S., Martin B. R., Compton D. R., et al. Identification of an Endogenous 2-Monoglyceride, Present in Canine Gut, That Binds to Cannabinoid Receptors. Biochem. Pharmacol. 1995 ; 50 (1). 83-90
7. Sugiura T., Kondo S., Sukagawa A., Nakane S., Shinoda A., Itoh K., Yamashita A., Waku K.. 2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain. Biochem. Biophys. Res. Commun. 1995 ; 215 (1). 89-97
8. Makara J. K., Mor M., Fegley D., Szabo S. I., Kathuria S., Astarita G., Duranti A., Tontini A., Tarzia G., Rivara S., et al. Selective Inhibition of 2-AG Hydrolysis Enhances Endocannabinoid Signaling in Hippocampus. Nat. Neurosci. 2005 ; 8 (9). 1139-1141
9. Bertrand T., Auge F., HouTmann J., Rak A., Vallee F., Mikol V., Berne P. F., Michot N., Cheuret D., Hoornaert C., et al. Structural Basis for Human Monoglyceride Lipase Inhibition. J. Mol. Biol. 2010 ; 396 (3). 663-673
10. Labar G., Bauvois C., Muccioli G. G., Wouters J., Lambert D. M.. Disulfiram Is an Inhibitor of Human Purified Monoacylglycerol Lipase, the Enzyme Regulating 2-Arachidonoylglycerol Signaling. Chembiochem. 2007 ; 8 (11). 1293-1297
11. Bode W., Mayr I., Baumann U., Huber R., Stone S. R., Hofsteenge J.. The Refined 1.9 A Crystal Structure of Human Alpha-Thrombin: Interaction with D-Phe-Pro-Arg Chloromethylketone and Significance of the Tyr-Pro-Pro-Trp Insertion Segment. EMBO J. 1989 ; 8 (11). 3467-3475
12. Desarnaud F., Cadas H., Piomelli D.. Anandamide Amidohydrolase Activity in Rat Brain Microsomes: Identification and Partial Characterization. J. Biol. Chem. 1995 ; 270 (11). 6030-6035
13. Vila A., Rosengarth A., Piomelli D., Cravatt B., Marnett L. J.. Hydrolysis of Prostaglandin Glycerol Esters by the Endocannabinoid-Hydrolyzing Enzymes, Monoacylglycerol Lipase and Fatty Acid Amide Hydrolase. Biochemistry. 2007 ; 46 (33). 9578-9585
14. Savinainen J. R., Yoshino M., Minkkila A., Nevalainen T., Laitinen J. T.. Characterization of Binding Properties of Monoglyceride Lipase Inhibitors by a Versatile Fluorescence-Based Technique. Anal. Biochem. 2010 ; 399 (1). 132-134
15. Schalk-Hihi C., Schubert C., Alexander R., Bayoumy S., Clemente J. C., Deckman I., DesJarlais R. L., Dzordzorme K. C., Flores C. M., Grasberger B., et al. Crystal Structure of a Soluble Form of Human Monoglyceride Lipase in Complex with an Inhibitor at 1.35 A Resolution. Protein Sci. 2011 ; 20 (4). 670-683
16. Kranz J. K., Schalk-Hihi C.. Protein Thermal Shifts to Identify Low Molecular Weight Fragments. Methods Enzymol. 2011 ; 493: 277-298
17. Matulis D., Kranz J. K., Salemme F. R., Todd M. J.. Thermodynamic Stability of Carbonic Anhydrase: Measurements of Binding Affinity and Stoichiometry Using ThermoFluor. Biochemistry. 2005 ; 44 (13). 5258-5266
18. Pantoliano M. W., Petrella E. C., Kwasnoski J. D., Lobanov V. S., Myslik J., Graf E., Carver T., Asel E., Springer B. A., Lane P., et al. High-Density Miniaturized Thermal Shift Assays as a General Strategy for Drug Discovery. J. Biomol. Screen. 2001 ; 6 (6). 429-440
19. Cummings M. D., Farnum M. A., Nelen M. I.. Universal Screening Methods and Applications of ThermoFluor. J. Biomol. Screen. 2006 ; 11 (7). 854-863
20. Huang H., Nishi K., Tsai H. J., Hammock B. D.. Development of Highly Sensitive Fluorescent Assays for Fatty Acid Amide Hydrolase. Anal. Biochem. 2007 ; 363 (1). 12-21
21. Kage K. L., Richardson P. L., Traphagen L., Severin J., Pereda-Lopez A., Lubben T., Davis-Taber R., Vos M. H., Bartley D., Walter K., et al. A High Throughput Fluorescent Assay for Measuring the Activity of Fatty Acid Amide Hydrolase. J. Neurosci. Methods. 2007 ; 161 (1). 47-54
22. Ramarao M. K., Murphy E. A., Shen M. W., Wang Y., Bushell K. N., Huang N., Pan N., Williams C., Clark J. D.. A Fluorescence-Based Assay for Fatty Acid Amide Hydrolase Compatible with High-Throughput Screening. Anal. Biochem. 2005 ; 343 (1). 143-151
23. Brandts J. F., Lin L. N.. Study of Strong to Ultratight Protein Interactions Using Differential Scanning Calorimetry. Biochemistry. 1990 ; 29 (29). 6927-6940
24. Morrison J. F.. Kinetics of the Reversible Inhibition of Enzyme-Catalysed Reactions by Tight-Binding Inhibitors. Biochim. Biophys. Acta. 1969 ; 185 (2). 269-286
25. Muccioli G. G., Labar G., Lambert D. M.. CAY10499, a Novel Monoglyceride Lipase Inhibitor Evidenced by an Expeditious MGL Assay. Chembiochem. 2008 ; 9 (16). 2704-2710
26. Wang Y., Chanda P., Jones P. G., Kennedy J. D.. A Fluorescence-Based Assay for Monoacylglycerol Lipase Compatible with Inhibitor Screening. Assay Drug Dev. Technol. 2008 ; 6 (3). 387-393