Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2.

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Title: Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2.
Authors: Haymer DH; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Duncan RA; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Rodriguez AL; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Han A; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Lindsay RJ; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Center for AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232, United States., Wijesiri NK; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Center for AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232, United States., Thompson Gray A; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Krishnan S; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Qi A; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Brown BP; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Center for AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232, United States., Boutaud O; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Engers DW; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States., Jones CK; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Niswender CM; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Lindsley CW; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Bender AM; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Source: Journal of medicinal chemistry [J Med Chem] 2026 Feb 26; Vol. 69 (4), pp. 4187-4207. Date of Electronic Publication: 2026 Feb 05.
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE; In Process
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  Data: <searchLink fieldCode="AU" term="%22Haymer+DH%22">Haymer DH</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Duncan+RA%22">Duncan RA</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Rodriguez+AL%22">Rodriguez AL</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Han+A%22">Han A</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Lindsay+RJ%22">Lindsay RJ</searchLink>; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Center for AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Wijesiri+NK%22">Wijesiri NK</searchLink>; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Center for AI in Protein Dynamics, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Thompson+Gray+A%22">Thompson Gray A</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Krishnan+S%22">Krishnan S</searchLink>; 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Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Engers+DW%22">Engers DW</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Jones+CK%22">Jones CK</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Niswender+CM%22">Niswender CM</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Lindsley+CW%22">Lindsley CW</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States.<br /><searchLink fieldCode="AU" term="%22Bender+AM%22">Bender AM</searchLink>; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.
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  Data: <searchLink fieldCode="JN" term="%229716531%22">Journal of medicinal chemistry</searchLink> [J Med Chem] 2026 Feb 26; Vol. 69 (4), pp. 4187-4207. <i>Date of Electronic Publication: </i>2026 Feb 05.
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