View source for 4frj


==Crystal structure of BACE1 in complex with aminooxazoline xanthene 9l==
<StructureSection load='4frj' size='340' side='right'caption='[[4frj]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4frj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FRJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DWB:(4S)-2-(5-CHLORO-2-FLUOROPHENYL)-7-METHOXYSPIRO[1,3-OXAZOLE-4,9-XANTHEN]-2-AMINE'>DWB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4frj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4frj OCA], [https://pdbe.org/4frj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4frj RCSB], [https://www.ebi.ac.uk/pdbsum/4frj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4frj ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human beta-secretase inhibitors. These compounds exhibited good enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound 11a resulted in a robust reduction of CNS Abeta40 in naive rats.

Structure and Property Based Design of Aminooxazoline Xanthenes as Selective and Orally Efficacious, CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer's Disease.,Huang H, La DS, Cheng AC, Whittington DA, Patel VF, Chen K, Dineen TA, Epstein O, Graceffa R, Hickman D, Kiang YH, Louie S, Luo Y, Wahl R, Wen P, Wood S, Fremeau B J Med Chem. 2012 Aug 28. PMID:22928914<ref>PMID:22928914</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4frj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Long AM]]
[[Category: Whittington DA]]