4i0f
From Proteopedia
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| - | {{STRUCTURE_4i0f| PDB=4i0f | SCENE= }} | ||
| - | ===Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors=== | ||
| - | {{ABSTRACT_PUBMED_23570791}} | ||
| - | == | + | ==Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors== |
| - | [[http://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN | + | <StructureSection load='4i0f' size='340' side='right'caption='[[4i0f]], [[Resolution|resolution]] 1.80Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4i0f]] 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=4I0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I0F 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BF:N-(6-CHLORO-3,3-DIMETHYL-3,4-DIHYDROISOQUINOLIN-1-YL)-3-[4-(1H-PYRAZOL-4-YL)THIOPHEN-3-YL]-L-ALANINE'>1BF</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=4i0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i0f OCA], [https://pdbe.org/4i0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i0f RCSB], [https://www.ebi.ac.uk/pdbsum/4i0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i0f ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Utilizing a structure based design approach, combined with extensive medicinal chemistry execution, highly selective, potent and novel BACE1 inhibitor 8 (BACE1 Alpha assay IC50=8nM) was made from a weak muM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed. | ||
| - | + | Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors.,Xu YZ, Yuan S, Bowers S, Hom RK, Chan W, Sham HL, Zhu YL, Beroza P, Pan H, Brecht E, Yao N, Lougheed J, Yan J, Tam D, Ren Z, Ruslim L, Bova MP, Artis DR Bioorg Med Chem Lett. 2013 May 15;23(10):3075-80. doi:, 10.1016/j.bmcl.2013.03.009. Epub 2013 Mar 21. PMID:23570791<ref>PMID:23570791</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | <div class="pdbe-citations 4i0f" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </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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