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Warren Foundation","award":["MH119673"],"award-info":[{"award-number":["MH119673"]}]},{"name":"William K. Warren Foundation","award":["MH062646"],"award-info":[{"award-number":["MH062646"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CB1 and CB2 cannabinoid receptors are members of the GPCR superfamily that modulate the effects of endocannabinoids. CB1 is the most abundant CB receptor in the central nervous system, while CB2 is present both peripherally and in the brain. CB2 plays a role in inflammation, as well as neurodegenerative and psychiatric disorders. To identify new ligands for CB2, we screened a library of FDA-approved drugs for activity at the receptor using a thallium flux assay, resulting in the discovery of the immunosuppressant mycophenolate mofetil as a potent, selective activator of CB2. Further characterization of the compound confirmed agonist activity in a variety of complementary assays, including PI hydrolysis, cAMP inhibition, and \u03b2-arrestin recruitment. Radioligand binding assays established a non-competitive interaction with the site occupied by [3H]CP55,940. CB2 agonists GW-842,166X and MDA7 were also profiled, revealing that GW-842,166X exhibits a similar activity profile to mycophenolate mofetil, whereas MDA7 presents a distinct profile. These differences provide insight into the complex CB2 pharmacology impacting preclinical and clinical studies, and ultimately, new treatment strategies for brain disorders.<\/jats:p>","DOI":"10.3390\/ijms26104956","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T13:59:43Z","timestamp":1747835983000},"page":"4956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Novel and Known Activators of Cannabinoid Receptor Subtype 2 Reveals Mixed Pharmacology That Differentiates Mycophenolate Mofetil and GW-842,166X from MDA7"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-5103","authenticated-orcid":false,"given":"Alice L.","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidong","family":"Qi","sequence":"additional","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allie","family":"Han","sequence":"additional","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley E.","family":"Kling","sequence":"additional","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of 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Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4182-2244","authenticated-orcid":false,"given":"David","family":"Whomble","sequence":"additional","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig W.","family":"Lindsley","sequence":"additional","affiliation":[{"name":"Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA"},{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Department of Chemistry, Vanderbilt 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