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Discovery of VU6025733 (AG06827): A Highly Selective, Orally Bioavailable, and Structurally Distinct M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) with Robust In Vivo Efficacy.

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Title: Discovery of VU6025733 (AG06827): A Highly Selective, Orally Bioavailable, and Structurally Distinct M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) with Robust In Vivo Efficacy.
Authors: Gregro AR; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Park C; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Long MF; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Baker LA; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Bollinger KA; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Ringuette AE; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Peng L; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Luscombe VB; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Billard NB; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, 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 School of Medicine, 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 School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Peng W; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Dickerson JW; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Rook JM; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., O'Neill J; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Chang S; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Boonen HCM; Neuroscience Drug Discovery Denmark, H. Lundbeck A/S, 9 Ottiliavej, Valby, Copenhagen DK-2500, Denmark., Jensen T; Neuroscience Drug Discovery Denmark, H. Lundbeck A/S, 9 Ottiliavej, Valby, Copenhagen DK-2500, Denmark., Thomsen MS; Neuroscience Drug Discovery Denmark, H. Lundbeck A/S, 9 Ottiliavej, Valby, Copenhagen DK-2500, Denmark., Bridges TM; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, 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 School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Conn PJ; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, 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 School of Medicine, 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 School of Medicine, Nashville, Tennessee 37232, United States.; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States., Temple KJ; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Vanderbilt Institute for Therapeutic Advances, Vanderbilt University, Nashville, Tennessee 37232, United States.
Source: ACS chemical neuroscience [ACS Chem Neurosci] 2026 Feb 04; Vol. 17 (3), pp. 649-665. Date of Electronic Publication: 2026 Jan 25.
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1948-7193
DOI:10.1021/acschemneuro.5c00963