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1. Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.

Author

Maccarrone, Mauro, Di Marzo, Vincenzo, Gertsch, Jürg, Grether, Uwe, Howlett, Allyn, Hua, Tian, Makriyannis, Alexandros, Piomelli, Daniele, Ueda, Natsuo, and van der Stelt, Mario

Subjects
Humans, Child, Endocannabinoids, Cannabidiol, Cannabinoids, Dronabinol, Cannabis, Carrier Proteins, Hallucinogens, Cannabinoid Receptor Agonists
Abstract

The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (∼3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research evidence and the Food and Drug Administration cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ9-tetrahydrocannabinol and other plant-derived cannabinoids (phytocannabinoids). Of note, our body has a complex endocannabinoid system (ECS)-made of receptors, metabolic enzymes, and transporters-that is also regulated by phytocannabinoids. The first endocannabinoid to be discovered 30 years ago was anandamide (N-arachidonoyl-ethanolamine); since then, distinct elements of the ECS have been the target of drug design programs aimed at curing (or at least slowing down) a number of human diseases, both in the central nervous system and at the periphery. Here a critical review of our knowledge of the goods and bads of the ECS as a therapeutic target is presented to define the benefits of ECS-active phytocannabinoids and ECS-oriented synthetic drugs for human health. SIGNIFICANCE STATEMENT: The endocannabinoid system plays important roles virtually everywhere in our body and is either involved in mediating key processes of central and peripheral diseases or represents a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of the components of this complex system, and in particular of key receptors (like cannabinoid receptors 1 and 2) and metabolic enzymes (like fatty acid amide hydrolase and monoacylglycerol lipase), will advance our understanding of endocannabinoid signaling and activity at molecular, cellular, and system levels, providing new opportunities to treat patients.

Published
2023

2. A monoacylglycerol lipase inhibitor showing therapeutic efficacy in mice without central side effects or dependence

Author

Jiang, Ming, Huizenga, Mirjam C. W., Wirt, Jonah L., Paloczi, Janos, Amedi, Avand, van den Berg, Richard J. B. H. N., Benz, Joerg, Collin, Ludovic, Deng, Hui, Di, Xinyu, Driever, Wouter F., Florea, Bogdan I., Grether, Uwe, Janssen, Antonius P. A., Hankemeier, Thomas, Heitman, Laura H., Lam, Tsang-Wai, Mohr, Florian, Pavlovic, Anto, Ruf, Iris, van den Hurk, Helma, Stevens, Anna F., van der Vliet, Daan, van der Wel, Tom, Wittwer, Matthias B., van Boeckel, Constant A. A., Pacher, Pal, Hohmann, Andrea G., and van der Stelt, Mario

Published
2023
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3. Structural basis of selective cannabinoid CB2 receptor activation

Author

Li, Xiaoting, Chang, Hao, Bouma, Jara, de Paus, Laura V., Mukhopadhyay, Partha, Paloczi, Janos, Mustafa, Mohammed, van der Horst, Cas, Kumar, Sanjay Sunil, Wu, Lijie, Yu, Yanan, van den Berg, Richard J. B. H. N., Janssen, Antonius P. A., Lichtman, Aron, Liu, Zhi-Jie, Pacher, Pal, van der Stelt, Mario, Heitman, Laura H., and Hua, Tian

Published
2023
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4. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes

Author

Alexander, Stephen PH, Fabbro, Doriano, Kelly, Eamonn, Mathie, Alistair, Peters, John A, Veale, Emma L, Armstrong, Jane F, Faccenda, Elena, Harding, Simon D, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Davies, Jamie A, Beuve, Annie, Boison, Detlev, Brouckaert, Peter, Burnett, John C, Burns, Kathryn, Dessauer, Carmen, Friebe, Andreas, Garthwaite, John, Gertsch, Jürg, Helsby, Nuala, Izzo, Angelo A, Koesling, Doris, Kuhn, Michaela, Ostrom, Rennolds, Papapetropoulos, Andreas, Potter, Lincoln R, Pyne, Nigel J, Pyne, Susan, Russwurm, Michael, Schmidt, Harald HHW, Seifert, Roland, Stasch, Johannes‐Peter, Szabo, Csaba, van der Stelt, Mario, van der Vliet, Albert, and Watts, Val

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Generic health relevance, Animals, Databases, Pharmaceutical, Enzyme Inhibitors, Humans, Hydrolases, Isomerases, Ligands, Ligases, Lyases, Oxidoreductases, Transferases, CGTP Collaborators, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14752. Enzymes are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2019

8. A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Author

van der Krift, Felix, primary, Zijlmans, Dick W, additional, Shukla, Rhythm, additional, Javed, Ali, additional, Koukos, Panagiotis I, additional, Schwarz, Laura LE, additional, Timmermans-Sprang, Elpetra PM, additional, Maas, Peter EM, additional, Gahtory, Digvijay, additional, van den Nieuwboer, Maurits, additional, Mol, Jan A, additional, Strous, Ger J, additional, Bonvin, Alexandre MJJ, additional, van der Stelt, Mario, additional, Veldhuizen, Edwin JA, additional, Weingarth, Markus, additional, Vermeulen, Michiel, additional, Klumperman, Judith, additional, and Maurice, Madelon M, additional

Published
2023
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11. Inhibition of diacylglycerol lipase β modulates lipid and endocannabinoid levels in the ex vivo human placenta

Author

Berger, Natascha, primary, van der Wel, Tom, additional, Hirschmugl, Birgit, additional, Baernthaler, Thomas, additional, Gindlhuber, Juergen, additional, Fawzy, Nermeen, additional, Eichmann, Thomas, additional, Birner-Gruenberger, Ruth, additional, Zimmermann, Robert, additional, van der Stelt, Mario, additional, and Wadsack, Christian, additional

Published
2023
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12. Oxygenation of Anandamide by Lipoxygenases

Author

Sub Cellular Protein Chemistry, Cellular Protein Chemistry, Maccarrone, Mauro, van Zadelhoff, Guus, van der Stelt, Mario, Sub Cellular Protein Chemistry, Cellular Protein Chemistry, Maccarrone, Mauro, van Zadelhoff, Guus, and van der Stelt, Mario

Published
2023

13. A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Author

Sub NMR Spectroscopy, Immunologie, Interne geneeskunde GD, CS_Cancer, Sub Biomol.Mass Spectrometry & Proteom., Infectious Diseases and Immunology - Immunology, van der Krift, Felix, Zijlmans, Dick W, Shukla, Rhythm, Javed, Ali, Koukos, Panagiotis I, Schwarz, Laura LE, Timmermans-Sprang, Elpetra Pm, Maas, Peter Em, Gahtory, Digvijay, van den Nieuwboer, Maurits, Mol, Jan A, Strous, Ger J, Bonvin, Alexandre Mjj, van der Stelt, Mario, Veldhuizen, Edwin Ja, Weingarth, Markus, Vermeulen, Michiel, Klumperman, Judith, Maurice, Madelon M, Sub NMR Spectroscopy, Immunologie, Interne geneeskunde GD, CS_Cancer, Sub Biomol.Mass Spectrometry & Proteom., Infectious Diseases and Immunology - Immunology, van der Krift, Felix, Zijlmans, Dick W, Shukla, Rhythm, Javed, Ali, Koukos, Panagiotis I, Schwarz, Laura LE, Timmermans-Sprang, Elpetra Pm, Maas, Peter Em, Gahtory, Digvijay, van den Nieuwboer, Maurits, Mol, Jan A, Strous, Ger J, Bonvin, Alexandre Mjj, van der Stelt, Mario, Veldhuizen, Edwin Ja, Weingarth, Markus, Vermeulen, Michiel, Klumperman, Judith, and Maurice, Madelon M

Published
2023

14. A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Author

CMM, CMM Groep Maurice, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, van der Krift, Felix, Zijlmans, Dick W., Shukla, Rhythm, Javed, Ali, Koukos, Panagiotis I., Schwarz, Laura L.E., Timmermans-Sprang, Elpetra P.M., Maas, Peter E.M., Gahtory, Digvijay, van den Nieuwboer, Maurits, Mol, Jan A., Strous, Ger J., Bonvin, Alexandre M.J.J., van der Stelt, Mario, Veldhuizen, Edwin J.A., Weingarth, Markus, Vermeulen, Michiel, Klumperman, Judith, Maurice, Madelon M., CMM, CMM Groep Maurice, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, van der Krift, Felix, Zijlmans, Dick W., Shukla, Rhythm, Javed, Ali, Koukos, Panagiotis I., Schwarz, Laura L.E., Timmermans-Sprang, Elpetra P.M., Maas, Peter E.M., Gahtory, Digvijay, van den Nieuwboer, Maurits, Mol, Jan A., Strous, Ger J., Bonvin, Alexandre M.J.J., van der Stelt, Mario, Veldhuizen, Edwin J.A., Weingarth, Markus, Vermeulen, Michiel, Klumperman, Judith, and Maurice, Madelon M.

Published
2023

15. Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition

Author

Ogasawara, Daisuke, Deng, Hui, Viader, Andreu, Baggelaar, Marc P., Breman, Arjen, den Dulk, Hans, van den Nieuwendijk, Adrianus M. C. H., Soethoudt, Marjolein, van der Wel, Tom, Zhou, Juan, Overkleeft, Herman S., Sanchez-Alavez, Manuel, Mori, Simone, Nguyen, William, Conti, Bruno, Liu, Xiaojie, Chen, Yao, Liu, Qing-song, Cravatt, Benjamin F., and van der Stelt, Mario

Published
2016

19. Plasma Levels of Endocannabinoids and Their Analogues Are Related to Specific Fecal Bacterial Genera in Young Adults: Role in Gut Barrier Integrity

Author

Ortiz-Alvarez, Lourdes, primary, Xu, Huiwen, additional, Di, Xinyu, additional, Kohler, Isabelle, additional, Osuna-Prieto, Francisco J., additional, Acosta, Francisco M., additional, Vilchez-Vargas, Ramiro, additional, Link, Alexander, additional, Plaza-Díaz, Julio, additional, van der Stelt, Mario, additional, Hankemeier, Thomas, additional, Clemente-Postigo, Mercedes, additional, Tinahones, Francisco J., additional, Gil, Angel, additional, Rensen, Patrick C. N., additional, Ruiz, Jonatan R., additional, and Martinez-Tellez, Borja, additional

Published
2022
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20. Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and in vivo efficacy

Author

Al Ayed, Karol, primary, Ballantine, Ross D., additional, Hoekstra, Michael, additional, Bann, Samantha J., additional, Wesseling, Charlotte M. J., additional, Bakker, Alexander T., additional, Zhong, Zheng, additional, Li, Yong-Xin, additional, Brüchle, Nora C., additional, van der Stelt, Mario, additional, Cochrane, Stephen A., additional, and Martin, Nathaniel I., additional

Published
2022
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21. Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe

Author

Gazzi, Thais, primary, Brennecke, Benjamin, additional, Atz, Kenneth, additional, Korn, Claudia, additional, Sykes, David, additional, Forn-Cuni, Gabriel, additional, Pfaff, Patrick, additional, Sarott, Roman C., additional, Westphal, Matthias V., additional, Mostinski, Yelena, additional, Mach, Leonard, additional, Wasinska-Kalwa, Malgorzata, additional, Weise, Marie, additional, Hoare, Bradley L., additional, Miljuš, Tamara, additional, Mexi, Maira, additional, Roth, Nicolas, additional, Koers, Eline J., additional, Guba, Wolfgang, additional, Alker, André, additional, Rufer, Arne C., additional, Kusznir, Eric A., additional, Huber, Sylwia, additional, Raposo, Catarina, additional, Zirwes, Elisabeth A., additional, Osterwald, Anja, additional, Pavlovic, Anto, additional, Moes, Svenja, additional, Beck, Jennifer, additional, Nettekoven, Matthias, additional, Benito-Cuesta, Irene, additional, Grande, Teresa, additional, Drawnel, Faye, additional, Widmer, Gabriella, additional, Holzer, Daniela, additional, van der Wel, Tom, additional, Mandhair, Harpreet, additional, Honer, Michael, additional, Fingerle, Jürgen, additional, Scheffel, Jörg, additional, Broichhagen, Johannes, additional, Gawrisch, Klaus, additional, Romero, Julián, additional, Hillard, Cecilia J., additional, Varga, Zoltan V., additional, van der Stelt, Mario, additional, Pacher, Pal, additional, Gertsch, Jürg, additional, Ullmer, Christoph, additional, McCormick, Peter J., additional, Oddi, Sergio, additional, Spaink, Herman P., additional, Maccarrone, Mauro, additional, Veprintsev, Dmitry B., additional, Carreira, Erick M., additional, Grether, Uwe, additional, and Nazaré, Marc, additional

Published
2022
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22. The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI-101 prevents cisplatin-induced nephrotoxicity

Author

Mukhopadhyay, Partha, Baggelaar, Marc, Erdelyi, Katalin, Cao, Zongxian, Cinar, Resat, Fezza, Filomena, Ignatowska-Janlowska, Bogna, Wilkerson, Jenny, van Gils, Noortje, Hansen, Thomas, Ruben, Marc, Soethoudt, Marjolein, Heitman, Laura, Kunos, George, Maccarrone, Mauro, Lichtman, Aron, Pacher, Pál, and Van der Stelt, Mario

Published
2016
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23. 2-AG-Mediated Control of GABAergic Signaling Is Impaired in a Model of Epilepsy.

Author

Colangeli, Roberto, Morena, Maria, Werner, Allison, Thompson, Roger J., van der Stelt, Mario, Pittman, Quentin J., Hill, Matthew N., and Teskey, G. Campbell

Subjects
MUSCARINIC acetylcholine receptors, LONG-term synaptic depression, EPILEPSY, NEUROPLASTICITY, NEURAL transmission, GABA
Abstract

Repeated seizures result in a persistent maladaptation of endocannabinoid (eCB) signaling, mediated part by anandamide signaling deficiency in the basolateral amygdala (BLA) that manifests as aberrant synaptic function and altered emotional behavior. Here, we determined the effect of repeated seizures (kindling) on 2-arachidonoylglycerol (2-AG) signaling on GABA transmission by directly measuring tonic and phasic eCB-mediated retrograde signaling in an in vitro BLA slice preparation from male rats. We report that both activity-dependent and muscarinic acetylcholine receptor (mAChR)-mediated depression of GABA synaptic transmission was reduced following repeated seizure activity. These effects were recapitulated in sham rats by preincubating slices with the 2-AG synthesizing enzyme inhibitor DO34. Conversely, preincubating slices with the 2-AG degrading enzyme inhibitor KML29 rescued activity-dependent 2-AG signaling, but not mAChR-mediated synaptic depression, over GABA transmission in kindled rats. These effects were not attributable to a change in cannabinoid type 1 (CB1) receptor sensitivity or altered 2-AG tonic signaling since the application of the highly selective CB1 receptor agonist CP55,940 provoked a similar reduction in GABA synaptic activity in both sham and kindled rats, while no effect of either DO34 or of the CB1 inverse agonist AM251 was observed on frequency and amplitude of spontaneous IPSCs in either sham or kindled rats. Collectively, these data provide evidence that repeated amygdala seizures persistently alter phasic 2-AG-mediated retrograde signaling at BLA GABAergic synapses, probably by impairing stimulus-dependent 2-AG synthesis/release, which contributes to the enduring aberrant synaptic plasticity associated with seizure activity. [ABSTRACT FROM AUTHOR]

Published
2023
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24. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes

Author

Alexander, Stephen P H, primary, Fabbro, Doriano, additional, Kelly, Eamonn, additional, Mathie, Alistair, additional, Peters, John A, additional, Veale, Emma L, additional, Armstrong, Jane F, additional, Faccenda, Elena, additional, Harding, Simon D, additional, Pawson, Adam J, additional, Southan, Christopher, additional, Davies, Jamie A, additional, Annett, Stephanie, additional, Boison, Detlev, additional, Burns, Kathryn Elisa, additional, Dessauer, Carmen, additional, Gertsch, Jürg, additional, Helsby, Nuala Ann, additional, Izzo, Angelo A., additional, Koesling, Doris, additional, Ostrom, Rennolds, additional, Papapetropoulos, Andreas, additional, Pyne, Nigel J., additional, Pyne, Susan, additional, Robson, Tracy, additional, Russwurm, Michael, additional, Seifert, Roland, additional, Stasch, Johannes‐Peter, additional, Szabo, Csaba, additional, van der Stelt, Mario, additional, van der Vliet, Albert, additional, Watts, Val, additional, and Wong, Szu Shen, additional

Published
2021
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26. The Chemical Biology-Medicinal Chemistry Continuum:EFMC's Vision

Author

Duca, Maria, Gillingham, Dennis, Olsen, Christian Adam, Sbardella, Gianluca, Skaanderup, Philip R., van der Stelt, Mario, Vauzeilles, Boris, Vazquez, Olalla, Auberson, Yves P., Duca, Maria, Gillingham, Dennis, Olsen, Christian Adam, Sbardella, Gianluca, Skaanderup, Philip R., van der Stelt, Mario, Vauzeilles, Boris, Vazquez, Olalla, and Auberson, Yves P.

Abstract

The European Federation for Medicinal chemistry and Chemical biology (EFMC) is a federation of learned societies. It groups organizations of European scientists working in a dynamic field spanning chemical biology and medicinal chemistry. New ideas, tools, and technologies emerging from a wide array of scientific disciplines continuously energize this rapidly evolving area. Medicinal chemistry is the design, synthesis, and optimization of biologically active molecules aimed at discovering new drug candidates – a mission that in many ways overlaps with the scope of chemical biology. Chemical biology is by now a mature field of science for which a more precise definition of what it encompasses, in the frame of EFMC, is timely. This article discusses chemical biology as currently understood by EFMC, including all activities dealing with the design and synthesis of biologically active chemical tools and their use to probe, characterize, or influence biological systems.

Published
2021

27. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors

Author

Alexander, Stephen PH, Christopoulos, Arthur, Davenport, Anthony P, Kelly, Eamonn, Mathie, Alistair, Peters, John A, Veale, Emma L, Armstrong, Jane F, Faccenda, Elena, Harding, Simon D, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Davies, Jamie A, Arumugam, Thiruma V, Bennett, Andrew, Sjogren, Benita, Sobey, Christopher, Wong, Szu Shen, Abbracchio, Maria P, Alexander, Wayne, Al-hosaini, Khaled, Back, Magnus, Beaulieu, Jean-Martin, Bernstein, Kenneth E, Bettler, Bernhard, Birdsall, Nigel JM, Blaho, Victoria, Bousquet, Corinne, Brauner-Osborne, Hans, Burnstock, Geoffrey, Calo, Girolamo, Castano, Justo P, Catt, Kevin J, Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chun, Jerold, Cianciulli, Antonia, Clapp, Lucie H, Couture, Rejean, Csaba, Zsolt, Dent, Gordon, Singh, Khuraijam Dhanachandra, Douglas, Steven D, Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward, Fong, Tung M, Fumagalli, Marta, Gainetdinov, Raul R, de Gasparo, Marc, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L, Goudet, Cyril, Gregory, Karen J, Gundlach, Andrew L, Hamann, Jorg, Hanson, Julien, Hauger, Richard L, Hay, Debbie, Heinemann, Akos, Hollenberg, Morley D, Holliday, Nicholas D, Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, Laszlo, Husain, Ahsan, Ijzerman, Adriaan P, Inagami, Tadashi, Jacobson, Kenneth A, Jensen, Robert T, Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kozielewicz, Pawel, Kreienkamp, Hans-Juergen, Kukkonen, Jyrki P, Langenhan, Tobias, Leach, Katie, Lecca, Davide, Lee, John D, Leeman, Susan E, Leprince, Jerome, Lolait, Stephen J, Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Mazella, Jean, McArdle, Craig A, Melmed, Shlomo, Michel, Martin C, Miller, Laurence, Mitolo, Vincenzo, Mouillac, Bernard, Murphy, Philip M, Nahon, Jean-Louis, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria A, Pertwee, Roger G, Pin, Jean-Philippe, Prossnitz, Eric, Ramachandran, Rithwik, Reinscheid, Rainer K, Rondard, Philippe, Rovati, G Enrico, Ruzza, Chiara, Sanger, Gareth, Schoeneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L, Serhan, Charles N, Stoddart, Leigh A, Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie, Thomas, Walter, Timmermans, Pieter BMWM, Tirupula, Kalyan, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S, Ward, Donald T, Wester, Hans-Juergen, Willars, Gary B, Williams, Tom Lloyd, Woodruff, Trent M, Yao, Chengcan, Aldrich, Richard W, Becirovic, Elvir, Biel, Martin, Catterall, William A, Conner, Alex C, Davies, Paul, Delling, Markus, Di Virgilio, Francesco, Falzoni, Simonetta, George, Chandy, Goldstein, Steve AN, Grissmer, Stephan, Ha, Kotdaji, Hammelmann, Verena, Hanukoglu, Israel, Jarvis, Mike, Jensen, Anders A, Kaczmarek, Leonard K, Kellenberger, Stephan, King, Brian, Lynch, Joseph W, Perez-Reyes, Edward, Plant, Leigh D, Rash, Lachlan D, Ren, Dejian, Sivilotti, Lucia G, Smart, Trevor G, Snutch, Terrance P, Tian, Jinbin, Van den Eynde, Charlotte, Vriens, Joris, Wei, Aguan D, Winn, Brenda T, Wulff, Heike, Xu, Haoxing, Yue, Lixia, Zhang, Xiaoli, Zhu, Michael, Coons, Laurel, Fuller, Peter, Korach, Kenneth S, Young, Morag, Bryant, Clare, Farndale, Richard W, Hobbs, Adrian, Jarvis, Gavin E, MacEwan, David, Monie, Tom P, Waldman, Scott, Beuve, Annie, Boison, Detlev, Brouckaert, Peter, Burnett, John C, Burns, Kathryn, Dessauer, Carmen, Friebe, Andreas, Garthwaite, John, Gertsch, Jurg, Helsby, Nuala, Izzo, Angelo A, Koesling, Doris, Kuhn, Michaela, Ostrom, Rennolds, Papapetropoulos, Andreas, Potter, Lincoln R, Pyne, Nigel J, Pyne, Susan, Russwurm, Michael, Schmidt, Harald HHW, Seifert, Roland, Stasch, Johannes-Peter, Szabo, Csaba, van der Stelt, Mario, van der Vliet, Albert, Watts, Val, Anderson, Catriona MH, Broer, Stefan, Dawson, Paul, Hagenbuch, Bruno, Hammond, James R, Hancox, Jules, Inui, Ken-ichi, Kanai, Yoshikatsu, Kemp, Stephan, Thwaites, David T, Verri, Tiziano, University of Nottingham, UK (UON), Monash university, University of Cambridge [UK] (CAM), University of Bristol [Bristol], University of Greenwich, Ninewells Hospital and Medical School [Dundee], University of Edinburgh, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Drug Design and Pharmacology [Copenhagen] (ILF), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Córdoba [Córdoba], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Institutes for BioMedical Research (NIBR), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), ARVALIS - Institut du végétal [Paris], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Glaxo Smith Kline [Harlow], University of Antwerp (UA), Neuroendocrinologie cellulaire et moléculaire, European Synchrotron Radiation Facility (ESRF), Experimental Medicine and Immunotherapeutics [Cambridge, UK], Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University [Riyadh] (KSU), Department of Cardiology, Karolinska University Hospital, Karolinska Institutet [Stockholm], Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Università degli Studi di Ferrara (UniFE), Department of Pharmacological Sciences and Biomolecular, University of Milan, Department of Molecular Biology Helen L. Dorris, The Scripps Research Institute, Département de Physiologie, Université de Montréal (UdeM), Department of Pharmacology, Université de Sherbrooke (UdeS), Departments of Physiology & Pharmacology, and Medicine [Calgary, Canada] (School of Medicine), University of Calgary, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Biochemistry, Medical Faculty, University of Leipzig, Department of Molecular and Biochemical Pharmacology, and Pleinlaan 2

Subjects
0301 basic medicine, RM, Databases, Pharmaceutical, Computer science, Drug classification, Pharmacology, Ligands, Receptors, G-Protein-Coupled, NO, law.invention, 03 medical and health sciences, Databases, G-Protein-Coupled, 0302 clinical medicine, law, Summary information, Receptors, Animals, Humans, Pharmacology & Pharmacy, The Concise Guide to Pharmacology 2019/20, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, Clinical pharmacology, Science & Technology, Extramural, POTENT, Pharmaceutical Preparations, 3. Good health, 030104 developmental biology, Pharmaceutical, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Catalytic receptors, Life Sciences & Biomedicine, 030217 neurology & neurosurgery
Abstract

© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2019

29. CB1 cannabinoid receptors and on-demand defense against excitotoxicity

Author

Marsicano, Giovanni, Goodenough, Sharon, Monory, Krisztina, Hermann, Heike, Eder, Matthias, Cannich, Astrid, Azad, Shanaz C., Cascio, Maria Grazia, Gutierrez, Silvia Ortega, van der Stelt, Mario, Lopez-Rodriguez, Maria Luz, Casanova, Emilio, Schutz, Gunther, Zieglgansberger, Walter, Di Marzo, Vincenzo, Behl, Christian, and Lutz, Beat

Subjects
Nervous system -- Research -- Physiological aspects -- Chemical properties, Cannabinoids -- Physiological aspects -- Research, Science and technology, Physiological aspects, Chemical properties, Research
Abstract

Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lad (expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice, the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons., Mnemonic processes and normal functioning of the brain require elevated neuronal activity. However, neuronal systems need to protect themselves against the risk of excessive activity, which could lead to pathological [...]

Published
2003

30. Discovery of N-(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases

Author

Zhang, Hongjun, primary, Lapointe, Blair T., additional, Anthony, Neville, additional, Azevedo, Rita, additional, Cals, Jos, additional, Correll, Craig C., additional, Daniels, Matthew, additional, Deshmukh, Sujal, additional, van Eenenaam, Hans, additional, Ferguson, Heidi, additional, Hegde, Laxminarayan G., additional, Karstens, Willem Jan, additional, Maclean, John, additional, Miller, J. Richard, additional, Moy, Lily Y., additional, Simov, Vladimir, additional, Nagpal, Sunil, additional, Oubrie, Arthur, additional, Palte, Rachel L., additional, Parthasarathy, Gopal, additional, Sciammetta, Nunzio, additional, van der Stelt, Mario, additional, Woodhouse, Janice D., additional, Trotter, B. Wesley, additional, and Barr, Kenneth, additional

Published
2020
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31. Stress-induced modulation of endocannabinoid signaling leads to delayed strengthening of synaptic connectivity in the amygdala

Author

Yasmin, Farhana, primary, Colangeli, Roberto, additional, Morena, Maria, additional, Filipski, Sarah, additional, van der Stelt, Mario, additional, Pittman, Quentin J., additional, Hillard, Cecilia J., additional, Teskey, G. Campbell, additional, McEwen, Bruce S., additional, Hill, Matthew N., additional, and Chattarji, Sumantra, additional

Published
2019
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32. Development of a Retinal-Based Probe for the Profiling of Retinaldehyde Dehydrogenases in Cancer Cells

Author

Koenders, Sebastiaan T. A., primary, Wijaya, Lukas S., additional, Erkelens, Martje N., additional, Bakker, Alexander T., additional, van der Noord, Vera E., additional, van Rooden, Eva J., additional, Burggraaff, Lindsey, additional, Putter, Pasquale C., additional, Botter, Else, additional, Wals, Kim, additional, van den Elst, Hans, additional, den Dulk, Hans, additional, Florea, Bogdan I., additional, van de Water, Bob, additional, van Westen, Gerard J. P., additional, Mebius, Reina E., additional, Overkleeft, Herman S., additional, Le Dévédec, Sylvia E., additional, and van der Stelt, Mario, additional

Published
2019
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33. Identification of α,β-Hydrolase Domain Containing Protein 6 as a Diacylglycerol Lipase in Neuro-2a Cells

Author

van Esbroeck, Annelot C. M., primary, Kantae, Vasudev, additional, Di, Xinyu, additional, van der Wel, Tom, additional, den Dulk, Hans, additional, Stevens, Anna F., additional, Singh, Simar, additional, Bakker, Alexander T., additional, Florea, Bogdan I., additional, Stella, Nephi, additional, Overkleeft, Herman S., additional, Hankemeier, Thomas, additional, and van der Stelt, Mario, additional

Published
2019
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35. High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue

Author

Kuipers, Eline N., primary, Kantae, Vasudev, additional, Maarse, Boukje C. Eveleens, additional, van den Berg, Susan M., additional, van Eenige, Robin, additional, Nahon, Kimberly J., additional, Reifel-Miller, Anne, additional, Coskun, Tamer, additional, de Winther, Menno P. J., additional, Lutgens, Esther, additional, Kooijman, Sander, additional, Harms, Amy C., additional, Hankemeier, Thomas, additional, van der Stelt, Mario, additional, Rensen, Patrick C. N., additional, and Boon, Mariëtte R., additional

Published
2019
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36. Gene Expression o Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight

Author

Nahon, Kimberly J., Nahon, Kimberly J., Kantae, Vasudev, den Haan, Roy, Hanssen, Mark J. W., Harms, Amy C., van der Stelt, Mario, Hankemeier, Thomas, Jazet, Ingrid M., van Marken Lichtenbelt, Wouter D., Rensen, Patrick C. N., Boon, Mariette R., Nahon, Kimberly J., Nahon, Kimberly J., Kantae, Vasudev, den Haan, Roy, Hanssen, Mark J. W., Harms, Amy C., van der Stelt, Mario, Hankemeier, Thomas, Jazet, Ingrid M., van Marken Lichtenbelt, Wouter D., Rensen, Patrick C. N., and Boon, Mariette R.

Abstract

Objective: The study aimed to investigate whether markers of endocannabinoid signaling differed between overweight men of South Asian and white Caucasian descent.Methods: We included South Asian (n=10) and white Caucasian (n =10) men with overweight and prediabetes aged 35 to 50 years. Plasma samples were analyzed for endocannabinoids, their congeners, and lipids. In white adipose tissue and skeletal muscle biopsies, mRNA expression of genes involved in the endocannabinoid system was assessed using quantitative RT-PCR. Fasting lipid oxidation and glucose oxidation were determined with indirect calorimetry.Results: Compared with white Caucasians, South Asians had higher levels of plasma 2-linoleoyl glycerol (PConclusions: Overweight South Asian men have higher plasma 2-linoleoyl glycerol and N-linoleoylethanolamine levels and lower gene expression of CB receptors and the endocannabinoid degradation enzyme FAAH2 in skeletal muscle compared with white Caucasians.

Published
2018

37. A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase

Author

Lahav, Daniël, Liu, Bing, van den Berg, Richard J B H N, van den Nieuwendijk, Adrianus M C H, Wennekes, Tom, Ghisaidoobe, Amar B T, Breen, Imogen, Ferraz, Maria Joao, Kuo, Chi-Lin, Wu, Liang, Geurink, Paul P, Ovaa, Huib, van der Marel, Gijsbert A, van der Stelt, Mario, Boot, Rolf G, Davies, Gideon J, Aerts, Johannes M F G, Overkleeft, Herman S., Sub Soft Condensed Matter, Afd Chemical Biology and Drug Discovery, Sub Algemeen Biologie, Chemical Biology and Drug Discovery, Sub Soft Condensed Matter, Afd Chemical Biology and Drug Discovery, Sub Algemeen Biologie, and Chemical Biology and Drug Discovery

Subjects
0301 basic medicine, Drug Evaluation, Preclinical, Fluorescence Polarization, Biochemistry, Article, Catalysis, law.invention, 03 medical and health sciences, 0302 clinical medicine, Colloid and Surface Chemistry, Glycolipid, GBA3, law, Hydrolase, Humans, Enzyme Inhibitors, Enzyme Assays, chemistry.chemical_classification, Chemistry, beta-Glucosidase, Activity-based proteomics, General Chemistry, Imino Sugars, Glucosylceramidase, Cytosol, 030104 developmental biology, Enzyme, 030220 oncology & carcinogenesis, Recombinant DNA
Abstract

Human nonlysosomal glucosylceramidase (GBA2) is one of several enzymes that controls levels of glycolipids and whose activity is linked to several human disease states. There is a major need to design or discover selective GBA2 inhibitors both as chemical tools and as potential therapeutic agents. Here, we describe the development of a fluorescence polarization activity-based protein profiling (FluoPol-ABPP) assay for the rapid identification, from a 350+ library of iminosugars, of GBA2 inhibitors. A focused library is generated based on leads from the FluoPol-ABPP screen and assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP on cell extracts containing recombinant, overexpressed glycosidase as the easily accessible enzyme source.

Published
2017

38. Cannabinoid CB receptor ligand profiling reveals biased signalling and off-target activity

Author

Soethoudt, Marjolein, Grether, Uwe, Fingerle, Jürgen, Grim, Travis W, Fezza, Filomena, de Petrocellis, Luciano, Ullmer, Christoph, Rothenhäusler, Benno, Perret, Camille, van Gils, Noortje, Finlay, David, MacDonald, Christa, Chicca, Andrea, Gens, Marianela Dalghi, Stuart, Jordyn, de Vries, Henk, Mastrangelo, Nicolina, Xia, Lizi, Alachouzos, Georgios, Baggelaar, Marc P, Martella, Andrea, Mock, Elliot D, Deng, Hui, Heitman, Laura H, Connor, Mark, Di Marzo, Vincenzo, Gertsch, Jürg, Lichtman, Aron H, Maccarrone, Mauro, Pacher, Pal, Glass, Michelle, van der Stelt, Mario, Hematology laboratory, Other Research, and General practice

Abstract

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.

Published
2017

39. Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight

Author

Nahon, Kimberly J., primary, Kantae, Vasudev, additional, den Haan, Roy, additional, Hanssen, Mark J.W., additional, Harms, Amy C., additional, van der Stelt, Mario, additional, Hankemeier, Thomas, additional, Jazet, Ingrid M., additional, van Marken Lichtenbelt, Wouter D., additional, Rensen, Patrick C.N., additional, and Boon, Mariëtte R., additional

Published
2018
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40. Chemical Proteomic Analysis of Serine Hydrolase Activity in Niemann-Pick Type C Mouse Brain

Author

van Rooden, Eva J., primary, van Esbroeck, Annelot C. M., additional, Baggelaar, Marc P., additional, Deng, Hui, additional, Florea, Bogdan I., additional, Marques, André R. A., additional, Ottenhoff, Roelof, additional, Boot, Rolf G., additional, Overkleeft, Herman S., additional, Aerts, Johannes M. F. G., additional, and van der Stelt, Mario, additional

Published
2018
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42. A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase

Author

Sub Soft Condensed Matter, Afd Chemical Biology and Drug Discovery, Sub Algemeen Biologie, Chemical Biology and Drug Discovery, Lahav, Daniël, Liu, Bing, van den Berg, Richard J B H N, van den Nieuwendijk, Adrianus M C H, Wennekes, Tom, Ghisaidoobe, Amar B T, Breen, Imogen, Ferraz, Maria Joao, Kuo, Chi-Lin, Wu, Liang, Geurink, Paul P, Ovaa, Huib, van der Marel, Gijsbert A, van der Stelt, Mario, Boot, Rolf G, Davies, Gideon J, Aerts, Johannes M F G, Overkleeft, Herman S., Sub Soft Condensed Matter, Afd Chemical Biology and Drug Discovery, Sub Algemeen Biologie, Chemical Biology and Drug Discovery, Lahav, Daniël, Liu, Bing, van den Berg, Richard J B H N, van den Nieuwendijk, Adrianus M C H, Wennekes, Tom, Ghisaidoobe, Amar B T, Breen, Imogen, Ferraz, Maria Joao, Kuo, Chi-Lin, Wu, Liang, Geurink, Paul P, Ovaa, Huib, van der Marel, Gijsbert A, van der Stelt, Mario, Boot, Rolf G, Davies, Gideon J, Aerts, Johannes M F G, and Overkleeft, Herman S.

Published
2017

43. Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474

Author

van Esbroeck, Annelot C M, Janssen, Antonius P A, Cognetta, Armand B, Ogasawara, Daisuke, Shpak, Guy, van der Kroeg, Mark, Kantae, Vasudev, Baggelaar, Marc P, de Vrij, Femke M S, Deng, Hui, Allarà, Marco, Fezza, Filomena, Lin, Zhanmin, van der Wel, Tom, Soethoudt, Marjolein, Mock, Elliot D, den Dulk, Hans, Baak, Ilse L, Florea, Bogdan I, Hendriks, Giel, De Petrocellis, Luciano, Overkleeft, Herman S, Hankemeier, Thomas, De Zeeuw, Chris I, Di Marzo, Vincenzo, Maccarrone, Mauro, Cravatt, Benjamin F, Kushner, Steven A, van der Stelt, Mario, van Esbroeck, Annelot C M, Janssen, Antonius P A, Cognetta, Armand B, Ogasawara, Daisuke, Shpak, Guy, van der Kroeg, Mark, Kantae, Vasudev, Baggelaar, Marc P, de Vrij, Femke M S, Deng, Hui, Allarà, Marco, Fezza, Filomena, Lin, Zhanmin, van der Wel, Tom, Soethoudt, Marjolein, Mock, Elliot D, den Dulk, Hans, Baak, Ilse L, Florea, Bogdan I, Hendriks, Giel, De Petrocellis, Luciano, Overkleeft, Herman S, Hankemeier, Thomas, De Zeeuw, Chris I, Di Marzo, Vincenzo, Maccarrone, Mauro, Cravatt, Benjamin F, Kushner, Steven A, and van der Stelt, Mario

Abstract

A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system.

Published
2017

46. Quantitative profiling of endocannabinoids and related N-acylethanolamines in human CSF using nano LC-MS/MS

Author

Kantae, Vasudev, primary, Ogino, Shinji, additional, Noga, Marek, additional, Harms, Amy C., additional, van Dongen, Robin M., additional, Onderwater, Gerrit L.J., additional, van den Maagdenberg, Arn M.J.M., additional, Terwindt, Gisela M., additional, van der Stelt, Mario, additional, Ferrari, Michel D., additional, and Hankemeier, Thomas, additional

Published
2017
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48. Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition

Author

Ogasawara, Daisuke, primary, Deng, Hui, additional, Viader, Andreu, additional, Baggelaar, Marc P., additional, Breman, Arjen, additional, den Dulk, Hans, additional, van den Nieuwendijk, Adrianus M. C. H., additional, Soethoudt, Marjolein, additional, van der Wel, Tom, additional, Zhou, Juan, additional, Overkleeft, Herman S., additional, Sanchez-Alavez, Manuel, additional, Mori, Simone, additional, Nguyen, William, additional, Conti, Bruno, additional, Liu, Xiaojie, additional, Chen, Yao, additional, Liu, Qing-song, additional, Cravatt, Benjamin F., additional, and van der Stelt, Mario, additional

Published
2015
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49. Identification of an allosteric binding site for RORγt inhibition

Author

Scheepstra, Marcel, primary, Leysen, Seppe, additional, van Almen, Geert C., additional, Miller, J. Richard, additional, Piesvaux, Jennifer, additional, Kutilek, Victoria, additional, van Eenennaam, Hans, additional, Zhang, Hongjun, additional, Barr, Kenneth, additional, Nagpal, Sunil, additional, Soisson, Stephen M., additional, Kornienko, Maria, additional, Wiley, Kristen, additional, Elsen, Nathaniel, additional, Sharma, Sujata, additional, Correll, Craig C., additional, Trotter, B. Wesley, additional, van der Stelt, Mario, additional, Oubrie, Arthur, additional, Ottmann, Christian, additional, Parthasarathy, Gopal, additional, and Brunsveld, Luc, additional

Published
2015
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