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

Wang, Hou, Liu, Li, Lin, Mukuo Wang, Shujing Hou, Ye Liu, Dongmei Li, Jianping Lin

Introduction i /G o protein) [ The G-protein-coupled receptors (GPCRs), containing about 800 members, are the largest membrane protein family known in the human body [ 1 ]. Although the expression of the CB1 receptor is low, both receptors exert a wide range of immune functions, such as regulating the release of cytokines [ 7 ]. In 2019, Li et al. [ 14 ] designed a high-affinity, CB2-receptor-specific antagonist AM10257 ( Figure 1 A) through systematic optimization of the CB1 receptor antagonist SR141716A (Rimonabant) [ 15 ], and the crystal structure of CB2 receptor in complex with AM10257 was resolved with a resolution of 2.80 Å. Markt et al. developed pharmacophore models based on CB2 receptor antagonists and identified seven compounds that showed Kvalues of <25 μM [ 19 ]. Chen et al. [ 20 ] constructed a 3D CB2 receptor homology structure model based on the crystal structure of bovine rhodopsin.

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