6uf0: Difference between revisions
From Proteopedia
Jump to navigationJump to search
m Protected "6uf0" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
==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
| ||||||||||||
