We are excited to co-author a new article published in the journal Science: “Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor”, resulting from a fruitful international collaboration involving:
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
- Graduate Program in Biophysics, University of California, San Francisco, San Francisco, CA, USA.
- Kobilka Institute of Innovative Drug Discovery, School of Life and Health Sciences, Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
- Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
- Enamine Ltd., 02094 Kyiv, Ukraine.
- Institute of Bioorganic Chemistry and Petrochemistry, National Ukrainian Academy of Science, 02660 Kyiv, Ukraine.
- National Taras Shevchenko University of Kyiv, 01601 Kyiv, Ukraine.
- Chemspace, Riga LV-1082, Latvia.
- National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
- Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
- Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
The article reports on discovering novel nonopioid analgesics from 301M REAL molecules in the ZINC15 library. A large-scale docking of virtual molecules to the α2A-adrenergic receptor binding site, followed by structure determination and studies in the lab, led to the identification of selective agonists that showed nanomolar activity without a sedative effect.
Many thanks to our colleague Dr. Natalia Tolmachova for representing Enamine in this study and to all the great collaborators:
Yurii Moroz, Elissa Fink, Jun Xu, Hübner Harald, Joao Braz, Philipp Seemann, Charlotte Avet, Veronica Craik, Dorothee Weikert, Maximilian F. Schmidt, , Chase Webb, Xi-Ping Huang, Chakrapani Kalyanaraman, Stefan Gahbauer, Ph.D., Geng Chen, Zheng Liu, Matthew P. Jacobson, John Irwin, Michel Bouvier, Yang Du, Brian Shoichet, Allan Basbaum, Peter Gmeiner
Get more information about REAL compounds by Enamine here: https://enamine.net/compound-collections/real-compounds/real-space-navigator