View source for 7myi


==BACE-1 in complex with compound #6==
<StructureSection load='7myi' size='340' side='right'caption='[[7myi]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYI 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]] 1.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZQS:(4aR,7aR)-6-(pyrimidin-2-yl)-7a-(thiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-amine'>ZQS</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=7myi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myi OCA], [https://pdbe.org/7myi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myi RCSB], [https://www.ebi.ac.uk/pdbsum/7myi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myi ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer's disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before development was terminated due to nonclinical retinal toxicity. LY2886721 advanced to Phase II, but development was halted due to abnormally elevated liver enzymes. Herein, we report the discovery and clinical development of LY3202626, a highly potent, CNS-penetrant, and low-dose BACE inhibitor, which successfully addressed these key development challenges.

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.,McKinzie DL, Winneroski LL, Green SJ, Hembre EJ, Erickson JA, Willis BA, Monk SA, Aluise CD, Baker TK, Lopez JE, Hendle J, Beck JP, Brier RA, Boggs LN, Borders AR, Cocke PJ, Garcia-Losada P, Lowe SL, Mathes BM, May PC, Porter WJ, Stout SL, Timm DE, Watson BM, Yang Z, Mergott DJ J Med Chem. 2021 Jun 24;64(12):8076-8100. doi: 10.1021/acs.jmedchem.1c00489. Epub, 2021 Jun 3. PMID:34081466<ref>PMID:34081466</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7myi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Hendle J]]
[[Category: Stout SL]]
[[Category: Timm DE]]