This presentation is to report the latest results in our modeling study on the key structural features of various literature-reported CB2R ligands as a new type of potential therapeutics for neurodegenerative diseases. Up-regulation of CB2R on activated microglial cells has been widely demonstrated as the first step in neurodegeneration. The receptor thereby is a promising target in the early diagnosis and treatment of a variety of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson disease. To date a large number of CB2R ligands with diverse scaffolds have been reported and the related structural features as well as the SARs are active subjects of medicinal chemistry research. Template-based alignment modeling (TAM) is a ligand-based approach developed recently in our modeling studies on opioid ligands. This innovative approach has proved to be rather effective in interpreting the complex SARs of opioid ligands (Wu and Hruby, ACS Omega, Oct. 2019). Inasmuch as both the opioids and the cannabinoids belong to the category of GPCR ligands, presumably TAM should be applicable with CB2R ligands as well. In this study, we employ TAM to explore the key structural features of the various CB2R ligands with regard to their binding selectivity and agonism vs. antagonism, as well as the possible structural correlations within the diverse ligands.

Template-based alignment modeling of the structure-activity relationships of CB2R ligands

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.