6uf0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==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== | |
| + | <StructureSection load='6uf0' size='340' side='right'caption='[[6uf0]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6uf0]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UF0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uf0 OCA], [http://pdbe.org/6uf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uf0 RCSB], [http://www.ebi.ac.uk/pdbsum/6uf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uf0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 6uf0" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Ankireddy, A]] | [[Category: Ankireddy, A]] | ||
| - | [[Category: | + | [[Category: David, B P]] |
| - | + | ||
| - | + | ||
[[Category: Dye, K]] | [[Category: Dye, K]] | ||
| - | [[Category: Lazzara, P | + | [[Category: Lazzara, P R]] |
| + | [[Category: Moore, T W]] | ||
| + | [[Category: Ratia, K M]] | ||
| + | [[Category: Reddy, S P]] | ||
| + | [[Category: Richardson, B G]] | ||
| + | [[Category: Keap1]] | ||
| + | [[Category: Nrf2 activator]] | ||
| + | [[Category: Protein binding]] | ||
| + | [[Category: Protein-protein interaction inhibitor]] | ||
Revision as of 07:59, 18 December 2019
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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