4i0g
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors== | |
| + | <StructureSection load='4i0g' size='340' side='right'caption='[[4i0g]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4i0g]] 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=4I0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I0G 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]] 1.78Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1B9:3-(4-BROMOTHIOPHEN-3-YL)-N-(6-CHLORO-3,3-DIMETHYL-3,4-DIHYDROISOQUINOLIN-1-YL)-L-ALANINE'>1B9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4i0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i0g OCA], [https://pdbe.org/4i0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i0g RCSB], [https://www.ebi.ac.uk/pdbsum/4i0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i0g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. | ||
| - | + | Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.,Bowers S, Xu YZ, Yuan S, Probst GD, Hom RK, Chan W, Konradi AW, Sham HL, Zhu YL, Beroza P, Pan H, Brecht E, Yao N, Lougheed J, Tam D, Ren Z, Ruslim L, Bova MP, Artis DR Bioorg Med Chem Lett. 2013 Apr 1;23(7):2181-6. doi: 10.1016/j.bmcl.2013.01.103., Epub 2013 Feb 4. PMID:23465612<ref>PMID:23465612</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4i0g" 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: Brecht E]] | ||
| + | [[Category: Yao N]] | ||
Current revision
Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors
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