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4DUS

Structure of Bace-1 (Beta-Secretase) in complex with N-((2S,3R)-1-(4-fluorophenyl)-3-hydroxy-4-((6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)butan-2-yl)acetamide

Summary for 4DUS
Entry DOI10.2210/pdb4dus/pdb
Related3RSV
DescriptorBeta-secretase 1, IODIDE ION, GLYCEROL, ... (5 entities in total)
Functional Keywordshydrolase, aspartyl protease, app, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationMembrane; Single-pass type I membrane protein: P56817
Total number of polymer chains1
Total formula weight47378.58
Authors
Sickmier, E.A. (deposition date: 2012-02-22, release date: 2012-10-10, Last modification date: 2024-10-09)
Primary citationKaller, M.R.,Harried, S.S.,Albrecht, B.,Amarante, P.,Babu-Khan, S.,Bartberger, M.D.,Brown, J.,Brown, R.,Chen, K.,Cheng, Y.,Citron, M.,Croghan, M.D.,Graceffa, R.,Hickman, D.,Judd, T.,Kriemen, C.,La, D.,Li, V.,Lopez, P.,Luo, Y.,Masse, C.,Monenschein, H.,Nguyen, T.,Pennington, L.D.,Miguel, T.S.,Sickmier, E.A.,Wahl, R.C.,Weiss, M.M.,Wen, P.H.,Williamson, T.,Wood, S.,Xue, M.,Yang, B.,Zhang, J.,Patel, V.,Zhong, W.,Hitchcock, S.
A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of beta-Secretase.
ACS Med Chem Lett, 3:886-891, 2012
Cited by
PubMed Abstract: β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.
PubMed: 24900403
DOI: 10.1021/ml3000148
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.5 Å)
Structure validation

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