4i0d

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{{STRUCTURE_4i0d| PDB=4i0d | SCENE= }}
 
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===Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors===
 
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{{ABSTRACT_PUBMED_23570791}}
 
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==Function==
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==Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors==
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[[http://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>
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<StructureSection load='4i0d' size='340' side='right'caption='[[4i0d]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4i0d]] 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=4I0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I0D FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1B7:N-(6-CHLORO-3,3-DIMETHYL-3,4-DIHYDROISOQUINOLIN-1-YL)-3-(4-PROPYLTHIOPHEN-3-YL)-L-ALANINE'>1B7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i0d OCA], [https://pdbe.org/4i0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i0d RCSB], [https://www.ebi.ac.uk/pdbsum/4i0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i0d ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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[[4i0d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I0D OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023570791</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4i0d" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
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[[Category: Large Structures]]
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[[Category: Brecht,E.]]
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[[Category: Brecht E]]
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[[Category: Yao, N.]]
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[[Category: Yao N]]
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[[Category: Aspartic protease]]
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[[Category: Bace]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Hydrolysis]]
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Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors

PDB ID 4i0d

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