4J0Z
CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH 5-Cyano-pyridine-2-carboxylic acid [3-((4S,5R)-2-amino-5-fluoro-4-fluoromethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide
Summary for 4J0Z
| Entry DOI | 10.2210/pdb4j0z/pdb |
| Related | 4J0P 4J0T 4J0V 4J0Y |
| Descriptor | Beta-secretase 1, SODIUM ION, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | protease inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P56817 |
| Total number of polymer chains | 1 |
| Total formula weight | 46067.45 |
| Authors | Kuglstatter, A.,Stihle, M. (deposition date: 2013-01-31, release date: 2013-05-01, Last modification date: 2024-10-30) |
| Primary citation | Hilpert, H.,Guba, W.,Woltering, T.J.,Wostl, W.,Pinard, E.,Mauser, H.,Mayweg, A.V.,Rogers-Evans, M.,Humm, R.,Krummenacher, D.,Muser, T.,Schnider, C.,Jacobsen, H.,Ozmen, L.,Bergadano, A.,Banner, D.W.,Hochstrasser, R.,Kuglstatter, A.,David-Pierson, P.,Fischer, H.,Polara, A.,Narquizian, R. beta-Secretase (BACE1) Inhibitors with High In Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer s Disease J.Med.Chem., 56:3980-3995, 2013 Cited by PubMed Abstract: An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pKa and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF Aβ40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of Aβ40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo. PubMed: 23590342DOI: 10.1021/jm400225m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.13 Å) |
Structure validation
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