8out
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==CRYSTAL STRUCTURE OF DLK IN COMPLEX WITH COMPOUND 22== | |
| + | <StructureSection load='8out' size='340' side='right'caption='[[8out]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8out]] 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=8OUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OUT 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]] 1.935Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W3C:(1R)-1-[4-[6-azanyl-5-(trifluoromethyloxy)pyridin-3-yl]-1-(3-fluoranyl-1-bicyclo[1.1.1]pentanyl)imidazol-2-yl]-2,2,2-tris(fluoranyl)ethanol'>W3C</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=8out FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8out OCA], [https://pdbe.org/8out PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8out RCSB], [https://www.ebi.ac.uk/pdbsum/8out PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8out ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet medical need with limited treatment options. Despite different mechanisms of action, diverse chemotherapeutics can cause CIPN through a converged pathway horizontal line an active axon degeneration program that engages the dual leucine zipper kinase (DLK). DLK is a neuronally enriched kinase upstream in the MAPK-JNK cascade, and while it is dormant under physiological conditions, DLK mediates a core mechanism for neuronal injury response under stress conditions, making it an attractive target for treatment of neuronal injury and neurodegenerative diseases. We have developed potent, selective, brain penetrant DLK inhibitors with excellent PK and activity in mouse models of CIPN. Lead compound IACS-52825 (22) showed strongly effective reversal of mechanical allodynia in a mouse model of CIPN and was advanced into preclinical development. | ||
| - | + | Discovery of IACS-52825, a Potent and Selective DLK Inhibitor for Treatment of Chemotherapy-Induced Peripheral Neuropathy.,Le K, Soth MJ, Cross JB, Liu G, Ray WJ, Ma J, Goodwani SG, Acton PJ, Buggia-Prevot V, Akkermans O, Barker J, Conner ML, Jiang Y, Liu Z, McEwan P, Warner-Schmidt J, Xu A, Zebisch M, Heijnen CJ, Abrahams B, Jones P J Med Chem. 2023 Jul 12. doi: 10.1021/acs.jmedchem.3c00788. PMID:37436942<ref>PMID:37436942</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8out" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Akkermans O]] | ||
| + | [[Category: Barker JJ]] | ||
| + | [[Category: Cross JB]] | ||
| + | [[Category: Zebisch M]] | ||
Revision as of 12:41, 26 July 2023
CRYSTAL STRUCTURE OF DLK IN COMPLEX WITH COMPOUND 22
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