The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans

• Published in: The Journal of neuroscience Vol. 35; no. 3; pp. 1199 - 1210
• Main Authors: May, Patrick C, Willis, Brian A, Lowe, Stephen L, Dean, Robert A, Monk, Scott A, Cocke, Patrick J, Audia, James E, Boggs, Leonard N, Borders, Anthony R, Brier, Richard A, Calligaro, David O, Day, Theresa A, Ereshefsky, Larry, Erickson, Jon A, Gevorkyan, Hykop, Gonzales, Celedon R, James, Douglas E, Jhee, Stanford S, Komjathy, Steven F, Li, Linglin, Lindstrom, Terry D, Mathes, Brian M, Martényi, Ferenc, Sheehan, Scott M, Stout, Stephanie L, Timm, David E, Vaught, Grant M, Watson, Brian M, Winneroski, Leonard L, Yang, Zhixiang, Mergott, Dustin J
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 21.01.2015
• Subjects: Alzheimer Disease - drug therapy; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Peptides - metabolism; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Animals; Aspartic Acid Endopeptidases - antagonists & inhibitors; Disease Models, Animal; Dogs; Heterocyclic Compounds, 2-Ring - pharmacokinetics; Heterocyclic Compounds, 2-Ring - pharmacology; Heterocyclic Compounds, 2-Ring - therapeutic use; Humans; Mice; Picolinic Acids - pharmacokinetics; Picolinic Acids - pharmacology; Picolinic Acids - therapeutic use; Protease Inhibitors - pharmacokinetics; Protease Inhibitors - pharmacology; Protease Inhibitors - therapeutic use; BACE1; clinical trial; nonclinical animal model; Alzheimer's disease; amyloid beta

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia a...