Identification of Novel Antagonists Targeting Cannabinoid Receptor 2 Using a Multi-Step Virtual Screening Strategy.

ABSTRACT: The endocannabinoid system plays an essential role in the regulation of analgesia and human immunity, and Cannabinoid Receptor 2 (CB2) has been proved to be an ideal target for the treatment of liver diseases and some cancers. In this study, we identified CB2 antagonists using a three-step "deep learning-pharmacophore-molecular docking" virtual screening approach. From the ChemDiv database (1,178,506 compounds), 15 hits were selected and tested by radioligand binding assays and cAMP functional assays. A total of 7 out of the 15 hits were found to exhibit binding affinities in the radioligand binding assays against CB2 receptor, with a pK_i of 5.15-6.66, among which five compounds showed antagonistic activities with pIC₅₀ of 5.25-6.93 in the cAMP functional assays. Amon

SUBMITTER: Wang M 

PROVIDER: S-EPMC8587544 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature