6uf0

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'''Unreleased structure'''
 
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The entry 6uf0 is ON HOLD until Paper Publication
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==Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain==
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<StructureSection load='6uf0' size='340' side='right'caption='[[6uf0]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6uf0]] is a 2 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=6UF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UF0 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]] 1.96&#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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Q5V:N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl](2,2,2-trifluoroethyl)amino}isoquinolin-1-yl)glycine'>Q5V</scene>, <scene name='pdbligand=Q5Y:N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine'>Q5Y</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=6uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uf0 OCA], [https://pdbe.org/6uf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uf0 RCSB], [https://www.ebi.ac.uk/pdbsum/6uf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uf0 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pharmacological activation of NRF2 (nuclear factor erythroid 2-related factor 2) arises from blocking the interaction of NRF2 with its negative regulator, KEAP1 (Kelch-like ECH-associated protein 1). We previously reported an isoquinoline-based NRF2 activator, but this compound showed negative logD7.4 and a -2 charge at physiological pH, which may have limited its membrane permeability. In this work, we report potent, metabolically stable analogs that result from replacing a carboxymethyl group at the 4-position with a fluoroalkyl group.
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Authors: Lazzara, P.R., David, B.P., Ankireddy, A., Richardson, B.G., Dye, K., Ratia, K.M., Reddy, S.P., Moore, T.W.
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Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability.,Lazzara PR, David BP, Ankireddy A, Richardson BG, Dye K, Ratia KM, Reddy SP, Moore TW J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01074. PMID:31682434<ref>PMID:31682434</ref>
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Description: Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Moore, T.W]]
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<div class="pdbe-citations 6uf0" style="background-color:#fffaf0;"></div>
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[[Category: David, B.P]]
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[[Category: Ankireddy, A]]
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==See Also==
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[[Category: Ratia, K.M]]
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*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]]
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[[Category: Richardson, B.G]]
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== References ==
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[[Category: Reddy, S.P]]
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<references/>
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[[Category: Dye, K]]
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__TOC__
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[[Category: Lazzara, P.R]]
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ankireddy A]]
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[[Category: David BP]]
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[[Category: Dye K]]
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[[Category: Lazzara PR]]
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[[Category: Moore TW]]
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[[Category: Ratia KM]]
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[[Category: Reddy SP]]
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[[Category: Richardson BG]]

Current revision

Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain

PDB ID 6uf0

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OCA

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