The First Photochromic Affinity Switch for the Human Cannabinoid Receptor 2. Issue 1 (5th February 2018)

• Record Type: Journal Article
• Authors: Dolles, Dominik; Strasser, Andrea; Wittmann, Hans‐Joachim; Marinelli, Oliviero; Nabissi, Massimo; Pertwee, Roger G.; Decker, Michael
• Is Part Of: Advanced therapeutics. Volume 1:Issue 1(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-02-05
• Subjects: azobenzene -- benzimidazole -- CB2 -- efficacy -- photopharmacology; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.201700032
• Languages: English
• ISSNs: 2366-3987

Abstract

Abstract: The h CB2 R plays an important in the immune system and is centrally expressed in microglia. The h CB2 R activated by agonists hold great therapeutic potential, e.g., in neuroinflammation. It is currently not yet elucidated how pathophysiological processes are mediated by the h CB2 R. Here, photochromic affinity switches based on a drugable benzimidazole core through azologization and computational studies are developed. Structure‐activity relationships (SARs) lead to compounds with high selectivity over h CB1 R that can be reversibly switched to a higher affinity cis ‐form proved on the receptor level by radioligand binding studies and translating into an affinity change in a functional GTPγS assay. cAMP ELISA and the change in expression level of two genes regulated by CREB proves that the compounds act as partial agonists. Abstract : Switching affinity : A highly h CB2 R‐selective benzimidazole changes solely affinity, but not efficacy, upon irradiation by UV.