Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche’s Endocannabinoid System Projects
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.
Authors
- Laura H. Heitman (ORCID: https://orcid.org/0000-0002-1381-8464)
- Ahmed Haider (ORCID: https://orcid.org/0000-0002-5204-4473)
- Giuseppe Campiani (ORCID: https://orcid.org/0000-0001-5295-9529)
- Dmitry B. Veprintsev (ORCID: https://orcid.org/0000-0002-3583-5409)
- Luca B. Gobbi (ORCID: https://orcid.org/0000-0002-0563-2491)
- Jürg Gertsch (ORCID: https://orcid.org/0000-0003-0978-1555)
- Daniel Hunziker
- Linjing Mu (ORCID: https://orcid.org/0000-0001-5354-1546)
- Stefania Butini (ORCID: https://orcid.org/0000-0002-8471-0880)
- Matthias Wittwer (ORCID: https://orcid.org/0000-0003-1359-4795)
- Wolfgang Guba (ORCID: https://orcid.org/0000-0002-3285-5957)
- Gisbert Schneider (ORCID: https://orcid.org/0000-0001-6706-1084)
- Kenneth Atz (ORCID: https://orcid.org/0000-0002-2628-1619)
- David A. Sykes (ORCID: https://orcid.org/0000-0002-6606-888X)
- Julián Romero (ORCID: https://orcid.org/0000-0002-2897-606X)
- Rainer E. Martin (ORCID: https://orcid.org/0000-0001-7895-497X)
- Javier Fernández‐Ruíz (ORCID: https://orcid.org/0000-0002-4490-0604)
- Erick M. Carreira (ORCID: https://orcid.org/0000-0003-1472-490X)
- Roger Schibli (ORCID: https://orcid.org/0000-0002-1537-3833)
- Fionn O’Hara
- Eva de Lago (ORCID: https://orcid.org/0000-0002-6260-3777)
- Thais Gazzi (ORCID: https://orcid.org/0000-0002-2321-6985)
- Uwe Grether (ORCID: https://orcid.org/0000-0002-3164-9270)
- Simon M. Ametamey
- Marc Nazaré (ORCID: https://orcid.org/0000-0002-1602-2330)
- Peter J. Mohr (ORCID: https://orcid.org/0000-0001-5068-3557)
- Ludovic Collin (ORCID: https://orcid.org/0000-0002-6313-3244)
- Antonia F. Stepan (ORCID: https://orcid.org/0000-0003-2203-129X)
- David F. Nippa (ORCID: https://orcid.org/0000-0002-0346-3786)
- Stephan Röver
- Bernd Kuhn (ORCID: https://orcid.org/0000-0002-4301-562X)
- Mario van der Stelt (ORCID: https://orcid.org/0000-0002-1029-5717)
- Sergio Oddi (ORCID: https://orcid.org/0000-0002-6217-698X)
- Hans Peter Märki
- Arne C. Rufer (ORCID: https://orcid.org/0000-0001-5092-7478)
- Pál Pacher (ORCID: https://orcid.org/0000-0001-7036-8108)
- Mauro Maccarrone (ORCID: https://orcid.org/0000-0002-3990-2963)
- Christoph Ullmer (ORCID: https://orcid.org/0000-0002-1044-6722)
- Julie Blaising (ORCID: https://orcid.org/0000-0002-3367-6184)
- Yingfang He (ORCID: https://orcid.org/0000-0002-2813-425X)
- Michael Honer
- Jörg Benz
- Jürgen Fingerle
- Johannes D. Aebi
Institutions
- University of Siena (IT)
- Roche (Switzerland) (CH)
- University of Bern (CH)
- Universidad Complutense de Madrid (ES)
- Leiden University (NL)
- University of Teramo (IT)
- University of Nottingham (GB)
- Universidad Francisco de Vitoria (ES)
- University of L'Aquila (IT)
- ETH Zurich (CH)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- Oncode Institute (NL)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- West Midlands Deanery (GB)
- Drug Discovery Laboratory (Norway) (NO)
- European Brain Research Institute (IT)
- University of Birmingham (GB)
Publication Details
- Journal
- CHIMIA International Journal for Chemistry
- Published
- 2024-08-21
- DOI
- https://doi.org/10.2533/chimia.2024.499
- Citations
- 4
- Primary Topic
- Cannabis and Cannabinoid Research
- Type
- article
- Field-Weighted Citation Impact
- 1.79
Funders
- F. Hoffmann-La Roche