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8bq4
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Phosphatidylinositol 5-Phosphate 4-Kinase (PI5P4K2C) bound to an inhibitor== | |
| + | <StructureSection load='8bq4' size='340' side='right'caption='[[8bq4]], [[Resolution|resolution]] 2.42Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8bq4]] 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=8BQ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BQ4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZR:6-methyl-~{N}-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine'>QZR</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=8bq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bq4 OCA], [https://pdbe.org/8bq4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bq4 RCSB], [https://www.ebi.ac.uk/pdbsum/8bq4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bq4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Owing to their central role in regulating cell signaling pathways, the phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive therapeutic targets in diseases such as cancer, neurodegeneration, and immunological disorders. Until now, tool molecules for these kinases have been either limited in potency or isoform selectivity, which has hampered further investigation of biology and drug development. Herein we describe the virtual screening workflow which identified a series of thienylpyrimidines as PI5P4Kgamma-selective inhibitors, as well as the medicinal chemistry optimization of this chemotype, to provide potent and selective tool molecules for further use. In vivo pharmacokinetics data are presented for exemplar tool molecules, along with an X-ray structure for ARUK2001607 (15) in complex with PI5P4Kgamma, along with its selectivity data against >150 kinases and a Cerep safety panel. | ||
| - | + | The Identification of Potent, Selective, and Brain Penetrant PI5P4Kgamma Inhibitors as In Vivo-Ready Tool Molecules.,Rooney TPC, Aldred GG, Boffey HK, Willems HMG, Edwards S, Chawner SJ, Scott DE, Green C, Winpenny D, Skidmore J, Clarke JH, Andrews SP J Med Chem. 2022 Dec 14. doi: 10.1021/acs.jmedchem.2c01693. PMID:36516442<ref>PMID:36516442</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Howard | + | <div class="pdbe-citations 8bq4" style="background-color:#fffaf0;"></div> |
| - | [[Category: Ogg | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Howard TD]] | ||
| + | [[Category: Ogg DJ]] | ||
Revision as of 09:09, 28 December 2022
Crystal Structure of Phosphatidylinositol 5-Phosphate 4-Kinase (PI5P4K2C) bound to an inhibitor
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