Search

Your search keyword '"Mock, Elliot D."' showing total 20 results
Start Over Author "Mock, Elliot D."
20 results on '"Mock, Elliot D."'

2. Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice

Author

Mock, Elliot D., Mustafa, Mohammed, Gunduz-Cinar, Ozge, Cinar, Resat, Petrie, Gavin N., Kantae, Vasudev, Di, Xinyu, Ogasawara, Daisuke, Varga, Zoltan V., Paloczi, Janos, Miliano, Cristina, Donvito, Giulia, van Esbroeck, Annelot C. M., van der Gracht, Anouk M. F., Kotsogianni, Ioli, Park, Joshua K., Martella, Andrea, van der Wel, Tom, Soethoudt, Marjolein, Jiang, Ming, Wendel, Tiemen J., Janssen, Antonius P. A., Bakker, Alexander T., Donovan, Colleen M., Castillo, Laura I., Florea, Bogdan I., Wat, Jesse, van den Hurk, Helma, Wittwer, Matthias, Grether, Uwe, Holmes, Andrew, van Boeckel, Constant A. A., Hankemeier, Thomas, Cravatt, Benjamin F., Buczynski, Matthew W., Hill, Matthew N., Pacher, Pal, Lichtman, Aron H., and van der Stelt, Mario

Published
2020
Full Text
View/download PDF

3. 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., and van der Stelt, Mario

Published
2017

7. Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

Author

Zhou, Juan, primary, Mock, Elliot D., additional, Al Ayed, Karol, additional, Di, Xinyu, additional, Kantae, Vasudev, additional, Burggraaff, Lindsey, additional, Stevens, Anna F., additional, Martella, Andrea, additional, Mohr, Florian, additional, Jiang, Ming, additional, van der Wel, Tom, additional, Wendel, Tiemen J., additional, Ofman, Tim P., additional, Tran, Yvonne, additional, de Koster, Nicky, additional, van Westen, Gerard J.P., additional, Hankemeier, Thomas, additional, and van der Stelt, Mario, additional

Published
2020
Full Text
View/download PDF

8. Activity-Based Protein Profiling Identifies α-Ketoamides as Inhibitors for Phospholipase A2 Group XVI

Author

Zhou, Juan, primary, Mock, Elliot D., additional, Martella, Andrea, additional, Kantae, Vasudev, additional, Di, Xinyu, additional, Burggraaff, Lindsey, additional, Baggelaar, Marc P., additional, Al-Ayed, Karol, additional, Bakker, Alexander, additional, Florea, Bogdan I., additional, Grimm, Sebastian H., additional, den Dulk, Hans, additional, Li, Chun T., additional, Mulder, Laura, additional, Overkleeft, Herman S., additional, Hankemeier, Thomas, additional, van Westen, Gerard J. P., additional, and van der Stelt, Mario, additional

Published
2019
Full Text
View/download PDF

10. 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

11. 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

12. ortho-Carborane-Modified N-Substituted Deoxynojirimycins

Author

Hoogendoorn, Sascha, Mock, Elliot D., Strijland, Anneke, Donker-Koopman, Wilma E., van den Elst, Hans, van den Berg, Richard J. B. H. N., Aerts, Johannes M. F. G., van der Marel, Gijsbert A., Overkleeft, Herman S., Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, and Medical Biochemistry

Abstract

N-alkyl-deoxynojirimycins (DNMs) are an important class of glycoprocessing enzyme inhibitors. Our work on DNMs focuses on identifying potent and selective inhibitors of the human enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA) and neutral glucosylceramidase (GBA2). We have previously reported on N-alkylated DNM derivatives bearing various hydrophobic head groups (aliphatic, aromatic, branched, cyclic). In this study we report effective procedures for the synthesis of ortho-carborane-modified DNMs and establish the inhibitory potency of six new DNM derivatives 3-8 against GCS, GBA and GBA2

Published
2015

14. Design of a Highly Selective Quenched Activity-Based Probe and Its Application in Dual Color Imaging Studies of Cathepsin S Activity Localization

Author

Oresic Bender, Kristina, primary, Ofori, Leslie, additional, van der Linden, Wouter A., additional, Mock, Elliot D., additional, Datta, Gopal K., additional, Chowdhury, Somenath, additional, Li, Hao, additional, Segal, Ehud, additional, Sanchez Lopez, Mateo, additional, Ellman, Jonathan A., additional, Figdor, Carl G., additional, Bogyo, Matthew, additional, and Verdoes, Martijn, additional

Published
2015
Full Text
View/download PDF

15. Incorporation of Non-natural Amino Acids Improves Cell Permeability and Potency of Specific Inhibitors of Proteasome Trypsin-like Sites

Author

Geurink, Paul P., primary, van der Linden, Wouter A., additional, Mirabella, Anne C., additional, Gallastegui, Nerea, additional, de Bruin, Gerjan, additional, Blom, Annet E. M., additional, Voges, Mathias J., additional, Mock, Elliot D., additional, Florea, Bogdan I., additional, van der Marel, Gijs A., additional, Driessen, Christoph, additional, van der Stelt, Mario, additional, Groll, Michael, additional, Overkleeft, Herman S., additional, and Kisselev, Alexei F., additional

Published
2013
Full Text
View/download PDF

18. Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

Author

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

Subjects
570 Life sciences, biology, 610 Medicine & health, 3. Good health
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.

19. Fluorescence-Based NAPE-PLD Activity Assay.

Author

Mock ED, Driever WPF, and van der Stelt M

Subjects
Humans, Fluorescence, HEK293 Cells, Endocannabinoids, Phospholipase D metabolism
Abstract

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the principal enzyme that generates N-acylethanolamines (NAEs), a family of signaling lipids that includes the endocannabinoid anandamide. To investigate the biological function and biosynthesis of NAEs, we sought to develop potent NAPE-PLD inhibitors. To this aim, we utilized a high-throughput screening-compatible NAPE-PLD activity assay, which uses the fluorescence-quenched substrate PED6. This assay conveniently uses membrane fractions of NAPE-PLD overexpressing HEK293T cell lysates, thus avoiding the need for protein purification. Here, we give a detailed description of the NAPE-PLD PED6 fluorescence activity assay, which has increased throughput compared to previous radioactivity- or mass-spectrometry-based assays., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
Full Text
View/download PDF

20. Cannabinoid CB 2 receptor ligand profiling reveals biased signalling and off-target activity.

Author

Soethoudt M, Grether U, Fingerle J, Grim TW, Fezza F, de Petrocellis L, Ullmer C, Rothenhäusler B, Perret C, van Gils N, Finlay D, MacDonald C, Chicca A, Gens MD, Stuart J, de Vries H, Mastrangelo N, Xia L, Alachouzos G, Baggelaar MP, Martella A, Mock ED, Deng H, Heitman LH, Connor M, Di Marzo V, Gertsch J, Lichtman AH, Maccarrone M, Pacher P, Glass M, and van der Stelt M

Subjects
Animals, Bridged Bicyclo Compounds pharmacology, CHO Cells, Cannabinoids pharmacology, Cell Line, Tumor, Cricetulus, Gene Expression, HEK293 Cells, High-Throughput Screening Assays, Humans, Keratinocytes cytology, Keratinocytes drug effects, Keratinocytes metabolism, Kinetics, Ligands, Macrophages cytology, Macrophages drug effects, Macrophages metabolism, Mice, Neurons cytology, Neurons metabolism, Protein Binding, Receptor, Cannabinoid, CB1 genetics, Receptor, Cannabinoid, CB2 genetics, Cannabinoid Receptor Agonists pharmacology, Neurons drug effects, Receptor, Cannabinoid, CB1 metabolism, Receptor, Cannabinoid, CB2 metabolism, Signal Transduction
Abstract

The cannabinoid CB 2 receptor (CB 2 R) 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 CB 2 R, 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 CB 2 R 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 CB 2 R agonists to study the role of CB 2 R 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., Competing Interests: Industry authors U.G., J.F., C.U., B.R. and C.P. are full-time employees of Hoffmann-La Roche and P.P. is full time employee of NIH. All academic authors state that they have no conflict of interest.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results