Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche’s Endocannabinoid System Projects

Authors

  • Johannes Aebi Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Kenneth Atz Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Simon M. Ametamey Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
  • Jörg Benz Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Julie Blaising Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Stefania Butini Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
  • Giuseppe Campiani Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
  • Erick M. Carreira Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zurich, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland
  • Ludovic Collin Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Eva de Lago Instituto Universitario de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
  • Thais Gazzi Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Jürg Gertsch Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland
  • Luca Gobbi Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Wolfgang Guba Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Javier Fernández-Ruiz Instituto Universitario de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
  • Jürgen Fingerle Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Ahmed Haider Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Yingfang He Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
  • Laura H. Heitman Division of Drug Discovery and Safety, Leiden University; Oncode Institute, Leiden, Netherlands
  • Michael Honer Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Daniel Hunziker Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Bernd Kuhn Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Mauro Maccarrone Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Italy; European Center for Brain Research, Santa Lucia Foundation, 00128 Rome, Italy
  • Hans Peter Märki Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Rainer E. Martin Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Peter Mohr Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Linjing Mu Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
  • Marc Nazaré Leibniz-Forschungsinstitut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany
  • David F. Nippa Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Sergio Oddi Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy; European, Center for Brain Research (CERC)/Santa Lucia Foundation, 00179 Rome, Italy
  • Fionn O’Hara Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Pal Pacher National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, United States of America
  • Julian Romero Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain
  • Stephan Röver Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Arne C. Rufer Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Roger Schibli Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
  • Gisbert Schneider ETH Zurich, Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
  • Antonia F. Stepan Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • David A. Sykes Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, England; United Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, England
  • Christoph Ullmer Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Mario van der Stelt Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands
  • Dmitry B. Veprintsev Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, England; United Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, England
  • Matthias B. Wittwer Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Uwe Grether Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel https://orcid.org/0000-0002-3164-9270

DOI:

https://doi.org/10.2533/chimia.2024.499

PMID:

39221845

Keywords:

Academia-industry collaboration, CB1R, CB2R, Endocannabinoid system, Labeled chemical probe, MAGL, PPAR

Abstract

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.

CHIMIA Vol. 78 No. 7-8 (2024): SCS Major Awards / SCS Fall Meeting 2024

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Published

2024-08-21

Issue

Vol. 78 No. 7-8 (2024): SCS Major Awards / SCS Fall Meeting 2024

Section

Scientific Articles

License

Copyright (c) 2024 Johannes Aebi, Kenneth Atz, Simon M. Ametamey, Jörg Benz, Julie Blaising, Stefania Butini, Giuseppe Campiani, Erick M. Carreira, Ludovic Collin, Eva de Lago, Thais Gazzi, Jürg Gertsch, Luca Gobbi, Wolfgang Guba, Javier Fernández-Ruiz, Jürgen Fingerle, Ahmed Haider, Yingfang He, Laura H. Heitman, Michael Honer, Daniel Hunziker, Bernd Kuhn, Mauro Maccarrone, Hans Peter Märki, Rainer E. Martin, Peter Mohr, Linjing Mu, Marc Nazaré, David F. Nippa, Sergio Oddi, Fionn O’Hara, Pal Pacher, Julian Romero, Stephan Röver, Arne C. Rufer, Roger Schibli, Gisbert Schneider, Antonia F. Stepan, David A. Sykes, Christoph Ullmer, Mario van der Stelt, Dmitry B. Veprintsev, Matthias B. Wittwer, Uwe Grether

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
J. Aebi, K. Atz, S. M. Ametamey, J. Benz, J. Blaising, S. Butini, G. Campiani, E. M. Carreira, L. Collin, E. de Lago, T. Gazzi, J. Gertsch, L. Gobbi, W. Guba, J. Fernández-Ruiz, J. Fingerle, A. Haider, Y. He, L. H. Heitman, M. Honer, D. Hunziker, B. Kuhn, M. Maccarrone, H. P. Märki, R. E. Martin, P. Mohr, L. Mu, M. Nazaré, D. F. Nippa, S. Oddi, F. O’Hara, P. Pacher, J. Romero, S. Röver, A. C. Rufer, R. Schibli, G. Schneider, A. F. Stepan, D. A. Sykes, C. Ullmer, M. van der Stelt, D. B. Veprintsev, M. B. Wittwer, U. Grether, Chimia 2024, 78, 499, DOI: 10.2533/chimia.2024.499.