Search

Your search keyword '"van der Stelt, Mario"' showing total 129 results
Start Over Author "van der Stelt, Mario" Publication Year Range Last 3 years
129 results on '"van der Stelt, Mario"'

1. Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria

Author

Bakker, Alexander T., Kotsogianni, Ioli, Avalos, Mariana, Punt, Jeroen M., Liu, Bing, Piermarini, Diana, Gagestein, Berend, Slingerland, Cornelis J., Zhang, Le, Willemse, Joost J., Ghimire, Leela B., van den Berg, Richard J. H. B. N., Janssen, Antonius P. A., Ottenhoff, Tom H. M., van Boeckel, Constant A. A., van Wezel, Gilles P., Ghilarov, Dmitry, Martin, Nathaniel I., and van der Stelt, Mario

Published
2024
Full Text
View/download PDF

2. 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

3. 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
Full Text
View/download PDF

4. 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
Full Text
View/download PDF

6. Multi-parameter optimization: Development of a morpholin-3-one derivative with an improved kinetic profile for imaging monoacylglycerol lipase in the brain

Author

He, Yingfang, Grether, Uwe, Taddio, Marco F., Meier, Carla, Keller, Claudia, Edelmann, Martin R., Honer, Michael, Huber, Sylwia, Wittwer, Matthias B., Heer, Dominik, Richter, Hans, Collin, Ludovic, Hug, Melanie N., Hilbert, Manuel, Postmus, Annemarieke G.J., Stevens, Anna Floor, van der Stelt, Mario, Krämer, Stefanie D., Schibli, Roger, Mu, Linjing, and Gobbi, Luca C.

Published
2022
Full Text
View/download PDF

10. Semisynthetic guanidino lipoglycopeptides with potent in vitro and in vivo antibacterial activity.

Author

van Groesen, Emma, Mons, Elma, Kotsogianni, Ioli, Arts, Melina, Tehrani, Kamaleddin H. M. E., Wade, Nicola, Lysenko, Vladyslav, Stel, Floor M., Zwerus, Jordy T., De Benedetti, Stefania, Bakker, Alexander, Chakraborty, Parichita, van der Stelt, Mario, Scheffers, Dirk-Jan, Gooskens, Jairo, Smits, Wiep Klaas, Holden, Kirsty, Gilmour, Peter S., Willemse, Joost, and Hitchcock, Christopher A.

Subjects
GRAM-positive bacterial infections, BACTERIAL cell walls, METHICILLIN-resistant staphylococcus aureus, GLYCOPEPTIDE antibiotics, ANTIBACTERIAL agents
Abstract

Gram-positive bacterial infections present a major clinical challenge, with methicillin- and vancomycin-resistant strains continuing to be a cause for concern. In recent years, semisynthetic vancomycin derivatives have been developed to overcome this problem as exemplified by the clinically used telavancin, which exhibits increased antibacterial potency but has also raised toxicity concerns. Thus, glycopeptide antibiotics with enhanced antibacterial activities and improved safety profiles are still necessary. We describe the development of a class of highly potent semisynthetic glycopeptide antibiotics, the guanidino lipoglycopeptides, which contain a positively charged guanidino moiety bearing a variable lipid group. These glycopeptides exhibited enhanced in vitro activity against a panel of Gram-positive bacteria including clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant strains, showed minimal toxicity toward eukaryotic cells, and had a low propensity for resistance selection. Mechanistically, guanidino lipoglycopeptides engaged with bacterial cell wall precursor lipid II with a higher binding affinity than vancomycin. Binding to both wild-type d-Ala-d-Ala lipid II and the vancomycin-resistant d-Ala-d-Lac variant was confirmed, providing insight into the enhanced activity of guanidino lipoglycopeptides against vancomycin-resistant isolates. The in vivo efficacy of guanidino lipoglycopeptide EVG7 was evaluated in a S. aureus murine thigh infection model and a 7-day sepsis survival study, both of which demonstrated superiority to vancomycin. Moreover, the minimal to mild kidney effects at supratherapeutic doses of EVG7 indicate an improved therapeutic safety profile compared with vancomycin. These findings position guanidino lipoglycopeptides as candidates for further development as antibacterial agents for the treatment of clinically relevant multidrug-resistant Gram-positive infections. Editor's summary: Vancomycin and its second-generation lipoglycopeptide derivatives work mainly by binding the peptidoglycan precursor lipid II to inhibit cell wall synthesis in Gram-positive bacteria. However, antibiotic resistance and safety concerns remain, and improved antibiotics are still needed. Van Groesen et al. report the optimization of a series of vancomycin-derived antibiotic compounds: lipoglycopeptides that bear a guanidino lipid group. This modification promoted stronger binding to the cell wall precursor lipid II, resulting in potent antibacterial activity while also showing less toxicity to mammalian cells than second-generation vancomycin derivatives. The lead candidate compound outperformed vancomycin in improving therapeutic outcome in mouse models of S. aureus thigh infection and sepsis, suggesting that guanidino lipoglycopeptides may benefit from further development. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

11. P2X7 receptor‐dependent increase in endocannabinoid 2‐arachidonoyl glycerol production by neuronal cells in culture: Dynamics and mechanism.

Author

Singh, Simar, Sarroza, Dennis, English, Anthony, Whittington, Dale, Dong, Ao, Malamas, Michael, Makriyannis, Alexandros, van der Stelt, Mario, Li, Yulong, Zweifel, Larry, Bruchas, Michael R., Land, Benjamin B., and Stella, Nephi

Subjects
CANNABINOID receptors, CELL culture, CONFOCAL fluorescence microscopy, PHOSPHOLIPASE C, GLYCERIN, NEUROLOGICAL disorders
Abstract

Background and Purpose: Neurotransmission and neuroinflammation are controlled by local increases in both extracellular ATP and the endocannabinoid 2‐arachidonoyl glycerol (2‐AG). While it is known that extracellular ATP stimulates 2‐AG production in cells in culture, the dynamics and molecular mechanisms that underlie this response remain poorly understood. Detection of real‐time changes in eCB levels with the genetically encoded sensor, GRABeCB2.0, can address this shortfall. Experimental Approach: 2‐AG and arachidonoylethanolamide (AEA) levels in Neuro2a (N2a) cells were measured by LC‐MS, and GRABeCB2.0 fluorescence changes were detected using live‐cell confocal microscopy and a 96‐well fluorescence plate reader. Key Results: 2‐AG and AEA increased GRABeCB2.0 fluorescence in N2a cells with EC50 values of 81 and 58 nM, respectively; both responses were reduced by the cannabinoid receptor type 1 (CB1R) antagonist SR141617 and absent in cells expressing the mutant‐GRABeCB2.0. ATP increased only 2‐AG levels in N2a cells, as measured by LC‐MS, and induced a transient increase in the GRABeCB2.0 signal within minutes primarily via activation of P2X7 receptors (P2X7R). This response was dependent on diacylglycerol lipase β activity, partially dependent on extracellular calcium and phospholipase C activity, but not controlled by the 2‐AG hydrolysing enzyme, α/β‐hydrolase domain containing 6 (ABHD6). Conclusions and Implications: Considering that P2X7R activation increases 2‐AG levels within minutes, our results show how these molecular components are mechanistically linked. The specific molecular components in these signalling systems represent potential therapeutic targets for the treatment of neurological diseases, such as chronic pain, that involve dysregulated neurotransmission and neuroinflammation. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

13. Discovery of a Cannabinoid CB2 Receptor Fluorescent Probe Based on a Pyridin-2-yl-benzyl-imidazolidine-2,4-dione Scaffold.

Author

de Paus, Laura V., Janssen, Antonius P.A., Halimi, Asad, van den Berg, Richard J. B. H. N., Heitman, Laura H., and van der Stelt, Mario

Subjects
FLUORESCENT probes, CANNABINOID receptors, MOLECULES, G protein coupled receptors, AMINATION, LIFE sciences
Abstract

This document discusses the development of a fluorescent probe, called compound 22, for the cannabinoid CB2 receptor. The probe was designed to visualize the receptor without the need for a toxic copper-mediated reaction. It demonstrated reasonable affinity for the CB2 receptor, selectivity over the CB1 receptor, and acted as an inverse agonist. The study also highlights the potential impact of small structural changes in compounds on the functional behavior of the CB2 receptor. This research contributes to the development of CB2 receptor-selective drugs for various applications. [Extracted from the article]

Published
2024
Full Text
View/download PDF

14. Development of Potent and Selective Monoacylglycerol Lipase Inhibitors. SARs, Structural Analysis, and Biological Characterization

Author

Butini, Stefania, primary, Grether, Uwe, additional, Jung, Kwang-Mook, additional, Ligresti, Alessia, additional, Allarà, Marco, additional, Postmus, Annemarieke G. J., additional, Maramai, Samuele, additional, Brogi, Simone, additional, Papa, Alessandro, additional, Carullo, Gabriele, additional, Sykes, David, additional, Veprintsev, Dmitry, additional, Federico, Stefano, additional, Grillo, Alessandro, additional, Di Guglielmo, Bruno, additional, Ramunno, Anna, additional, Stevens, Anna Floor, additional, Heer, Dominik, additional, Lamponi, Stefania, additional, Gemma, Sandra, additional, Benz, Jörg, additional, Di Marzo, Vincenzo, additional, van der Stelt, Mario, additional, Piomelli, Daniele, additional, and Campiani, Giuseppe, additional

Published
2024
Full Text
View/download PDF

16. IMI European Lead Factory — democratizing access to high-throughput screening

Author

Jones, Philip S., Boucharens, Sylviane, McElroy, Stuart P., Morrison, Angus, Honarnejad, Saman, van Boeckel, Stan, van den Hurk, Helma, Basting, Daniel, Hüser, Jörg, Jaroch, Stefan, Ottow, Eckhard, Benningshof, Jorg, Folmer, Rutger H. A., Leemhuis, Frank, Kramer-Verhulst, Patricia M., Nies, Vera J. M., Orrling, Kristina M., Rijnders, Ton, Pfander, Claudia, Engkvist, Ola, Pairaudeau, Garry, Simpson, Peter B., Ortholand, Jean-Yves, Roche, Didier, Dömling, Alexander, Kühnert, Sven M., Roevens, Peter W. M., van Vlijmen, Herman, van Wanrooij, Eva J. A., Verbruggen, Christophe, Nussbaumer, Peter, Ovaa, Huib, van der Stelt, Mario, Simonsen, Klaus Baek, Tagmose, Lena, Waldmann, Herbert, Duffy, James, Finsinger, Dirk, Jurzak, Mirek, Burgess-Brown, Nicola A., Lee, Wen H., Rutjes, Floris P. J. T., Haag, Hubert, Kallus, Christopher, Mors, Hartmut, Dorval, Thierry, Lesur, Brigitte, Ramon Olayo, Fernando, Hamza, Daniel, Jones, Geraint, Pearce, Christopher, Piechot, Alexander, Tzalis, Dimitrios, Clausen, Mads H., Davis, Jeremy, Derouane, Daphné, Vermeiren, Céline, Kaiser, Markus, Stockman, Robert A., Barrault, Denise V., Pannifer, Andrew D., Swedlow, Jason R., Nelson, Adam S., Orru, Romano V. A., Ruijter, Eelco, van Helden, Steven P., Li, Volkhart M., Vries, Ton, and de Vlieger, Jon S. B.

Published
2022
Full Text
View/download PDF

18. Biochemical and Cellular Characterization of the Function of Fluorophosphonate-Binding Hydrolase H (FphH) in Staphylococcus aureus Support a Role in Bacterial Stress Response

Author

Fellner, Matthias, primary, Walsh, Annabel, additional, Dela Ahator, Stephen, additional, Aftab, Nadia, additional, Sutherland, Ben, additional, Tan, Eng W., additional, Bakker, Alexander T., additional, Martin, Nathaniel I., additional, van der Stelt, Mario, additional, and Lentz, Christian S., additional

Published
2023
Full Text
View/download PDF

19. Structural basis of selective cannabinoid CB2 receptor activation

Author

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

Published
2023
Full Text
View/download PDF

20. 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
Full Text
View/download PDF

22. Disruption of tonic endocannabinoid signalling triggers cellular, behavioural and neuroendocrine responses consistent with a stress response.

Author

Petrie, Gavin N., Balsevich, Georgia, Füzesi, Tamás, Aukema, Robert J., Driever, Wouter P. F., van der Stelt, Mario, Bains, Jaideep S., and Hill, Matthew N.

Subjects
CORTICOTROPIN releasing hormone, HYPOTHALAMUS, CELL communication, HYPOTHALAMIC-pituitary-adrenal axis, PARAVENTRICULAR nucleus
Abstract

Background and Purpose: Endocannabinoid (eCB) signalling gates many aspects of the stress response, including the hypothalamic--pituitary--adrenal (HPA) axis. The HPA axis is controlled by corticotropin releasing hormone (CRH) producing neurons in the paraventricular nucleus of the hypothalamus (PVN). Disruption of eCB signalling increases drive to the HPA axis, but the mechanisms subserving this process are poorly understood. Experimental Approach: Using an array of cellular, endocrine and behavioural readouts associated with activation of CRH neurons in the PVN, we evaluated the contributions of tonic eCB signalling to the generation of a stress response. Key Results: The CB1 receptor antagonist/inverse agonist AM251, neutral antagonist NESS243 and NAPE PLD inhibitor LEI401 all uniformly increased Fos in the PVN, unmasked stress-linked behaviours, such as grooming, and increased circulating CORT, recapitulating the effects of stress. Similar effects were also seen after direct administration of AM251 into the PVN, while optogenetic inhibition of PVN CRH neurons ameliorated stress-like behavioural changes produced by disruption of eCB signalling. Conclusions and Implications: These data indicate that under resting conditions, constitutive eCB signalling restricts activation of the HPA axis through local regulation of CRH neurons in the PVN. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

24. 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
Full Text
View/download PDF

26. 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

27. 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

28. 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

29. EFMC – Trends that Link Medicinal Chemistry and Chemical Biology to Translational Drug Discovery

Author

Auberson, Yves P., primary, Arimondo, Paola B., additional, Duca, Maria, additional, Essig, Sebastian, additional, Grether, Uwe, additional, Rufer, Arne C., additional, Sbardella, Gianluca, additional, Schopfer, Ulrich, additional, Torrens, Antoni, additional, van der Stelt, Mario, additional, Vauzeilles, Boris, additional, Vázquez, Olalla, additional, and Zhang, Andrew X., additional

Published
2023
Full Text
View/download PDF

31. Chemical Proteomics Reveals Antibiotic Targets of Oxadiazolones in MRSA

Author

Bakker, Alexander T., primary, Kotsogianni, Ioli, additional, Mirenda, Liza, additional, Straub, Verena M., additional, Avalos, Mariana, additional, van den Berg, Richard J. B. H. N., additional, Florea, Bogdan I., additional, van Wezel, Gilles P., additional, Janssen, Antonius P. A., additional, Martin, Nathaniel I., additional, and van der Stelt, Mario, additional

Published
2022
Full Text
View/download PDF

33. EFMC - trends that link medicinal chemistry and chemical biology to translational drug discovery

Author

Auberson, Yves P., Arimondo, Paola B., Duca, Maria, Essig, Sebastian, Grether, Uwe, Rufer, Arne C., Sbardella, Gianluca, Schopfer, Ulrich, Torrens, Antoni, van der Stelt, Mario, Vauzeilles, Boris, Vázquez, Olalla, and Zhang, Andrew X.

Abstract

Ground-breaking research in disease biology and continuous efforts in method development have uncovered a range of potential new drug targets. Increasingly, the drug discovery process is informed by technologies involving chemical probes as tools. Applications for chemical probes comprise target identification and assessment, as well as the qualification of small molecules as chemical starting points and drug candidates. Progress in probe chemistry has opened the way to novel assay formats and pharmaceutical compound classes. The European Federation of Medicinal Chemistry and Chemical Biology (EFMC) has launched the Chemical Biology Initiative to advance science in the field of medicinal chemistry and chemical biology, while representing all members of this extended scientific community. This review provides an overview of the many important developments in the field of chemical biology that have happened at the lively interface of academic and industrial research.

Published
2023

34. Goods and bads of endocannabinoid system as a therapeutic target: Lessons learned after 30 years

Author

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

Subjects
610 Medizin und Gesundheit, 570 Biowissenschaften, Biologie
Abstract

The cannabis derivative marijuana is the most widely used recreational drug in the Western world, that 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 USA and worldwide. Compelling research evidence and the FDA cannabis-derived cannabidiol approval for severe childhood epilepsy have confirmed the large therapeutic potential of cannabidiol itself, Δ9-tetrahydrocannabinol (THC) 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 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 ECS as a therapeutic target are presented, in order to define the benefits of ECS-active phytocannabinoids and ECS-oriented synthetic drugs for human health. Significance Statement The endocannabinoid system plays important roles everywhere in our body and is either involved in mediating key processes of central and peripheral diseases or represents a therapeutic target for treatment. Understanding structure, function, and pharmacology of the components of this complex system, and in particular of key receptors (like CB1R and CB2R) and metabolic enzymes (like FAAH and MAGL), will advance our understanding of endocannabinoid signaling and activity at molecular, cellular, and system levels providing new opportunities to treat patients.

Published
2023
Full Text
View/download PDF

36. Comparative Photoaffinity Profiling of Omega-3 Signaling Lipid Probes Reveals Prostaglandin Reductase 1 as a Metabolic Hub in Human Macrophages

Author

Gagestein, Berend, primary, von Hegedus, Johannes H., additional, Kwekkeboom, Joanneke C., additional, Heijink, Marieke, additional, Blomberg, Niek, additional, van der Wel, Tom, additional, Florea, Bogdan I., additional, van den Elst, Hans, additional, Wals, Kim, additional, Overkleeft, Herman S., additional, Giera, Martin, additional, Toes, René E. M., additional, Ioan-Facsinay, Andreea, additional, and van der Stelt, Mario, additional

Published
2022
Full Text
View/download PDF

38. Live‐Cell Imaging of Sterculic Acid—a Naturally Occurring 1,2‐Cyclopropene Fatty Acid—by Bioorthogonal Reaction with Turn‐On Tetrazine‐Fluorophore Conjugates**

Author

Bertheussen, Kristine, primary, van de Plassche, Merel, additional, Bakkum, Thomas, additional, Gagestein, Berend, additional, Ttofi, Iakovia, additional, Sarris, Alexi J. C., additional, Overkleeft, Herman S., additional, van der Stelt, Mario, additional, and van Kasteren, Sander I., additional

Published
2022
Full Text
View/download PDF

39. 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
Full Text
View/download PDF

44. Employing Sterculic Acid – a naturally occurring 1,2-cyclopropene fatty acid – for live-cell imaging of lipids by inverse electron-demand Diels-Alder reaction

Author

Bertheussen, Kristine, primary, van de Plassche, Merel, additional, Bakkum, Thomas, additional, Gagestein, Berend, additional, Ttofi, Iakovia, additional, Sarris, Alexi, additional, Overkleeft, Herman, additional, van der Stelt, Mario, additional, and van Kasteren, Sander, additional

Published
2022
Full Text
View/download PDF

45. 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, additional, Wesseling, Charlotte, additional, Bakker, Alexander, additional, Zhong, Zheng, additional, Li, Yongxin, additional, van der Stelt, Mario, additional, Cochrane, Stephen, additional, and Martin, Nathaniel, additional

Published
2022
Full Text
View/download PDF

46. 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
Full Text
View/download PDF

47. Plasma Levels of Endocannabinoids and Their Analogues Are Related to Specific Fecal Bacterial Genera in Young Adults: Role on 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-Madueño, Francisco J., additional, Gil, Angel, additional, Rensen, Patrick C.N., additional, Ruiz, Jonatan R., additional, and Martinez-Tellez, Borja, additional

Published
2022
Full Text
View/download PDF

48. 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
Full Text
View/download PDF

49. IMI European Lead Factory — democratizing access to high-throughput screening

Author

Jones, Philip S., primary, Boucharens, Sylviane, additional, McElroy, Stuart P., additional, Morrison, Angus, additional, Honarnejad, Saman, additional, van Boeckel, Stan, additional, van den Hurk, Helma, additional, Basting, Daniel, additional, Hüser, Jörg, additional, Jaroch, Stefan, additional, Ottow, Eckhard, additional, Benningshof, Jorg, additional, Folmer, Rutger H. A., additional, Leemhuis, Frank, additional, Kramer-Verhulst, Patricia M., additional, Nies, Vera J. M., additional, Orrling, Kristina M., additional, Rijnders, Ton, additional, Pfander, Claudia, additional, Engkvist, Ola, additional, Pairaudeau, Garry, additional, Simpson, Peter B., additional, Ortholand, Jean-Yves, additional, Roche, Didier, additional, Dömling, Alexander, additional, Kühnert, Sven M., additional, Roevens, Peter W. M., additional, van Vlijmen, Herman, additional, van Wanrooij, Eva J. A., additional, Verbruggen, Christophe, additional, Nussbaumer, Peter, additional, Ovaa, Huib, additional, van der Stelt, Mario, additional, Simonsen, Klaus Baek, additional, Tagmose, Lena, additional, Waldmann, Herbert, additional, Duffy, James, additional, Finsinger, Dirk, additional, Jurzak, Mirek, additional, Burgess-Brown, Nicola A., additional, Lee, Wen H., additional, Rutjes, Floris P. J. T., additional, Haag, Hubert, additional, Kallus, Christopher, additional, Mors, Hartmut, additional, Dorval, Thierry, additional, Lesur, Brigitte, additional, Ramon Olayo, Fernando, additional, Hamza, Daniel, additional, Jones, Geraint, additional, Pearce, Christopher, additional, Piechot, Alexander, additional, Tzalis, Dimitrios, additional, Clausen, Mads H., additional, Davis, Jeremy, additional, Derouane, Daphné, additional, Vermeiren, Céline, additional, Kaiser, Markus, additional, Stockman, Robert A., additional, Barrault, Denise V., additional, Pannifer, Andrew D., additional, Swedlow, Jason R., additional, Nelson, Adam S., additional, Orru, Romano V. A., additional, Ruijter, Eelco, additional, van Helden, Steven P., additional, Li, Volkhart M., additional, Vries, Ton, additional, and de Vlieger, Jon S. B., additional

Published
2021
Full Text
View/download PDF

50. 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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results