8vew
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 24== | |
| + | <StructureSection load='8vew' size='340' side='right'caption='[[8vew]], [[Resolution|resolution]] 2.69Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8vew]] 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=8VEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VEW 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]] 2.69Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AAU:5-{2-[(2R,5S)-5-methyl-2-phenylpiperidin-1-yl](oxo)acetamido}pyridine-3-carboxamide'>A1AAU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</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=8vew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vew OCA], [https://pdbe.org/8vew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vew RCSB], [https://www.ebi.ac.uk/pdbsum/8vew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vew ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | It has been shown that PRMT5 inhibition by small molecules can selectively kill cancer cells with homozygous deletion of the MTAP gene if the inhibitors can leverage the consequence of MTAP deletion, namely, accumulation of the MTAP substrate MTA. Herein, we describe the discovery of TNG908, a potent inhibitor that binds the PRMT5.MTA complex, leading to 15-fold-selective killing of MTAP-deleted (MTAP-null) cells compared to MTAPintact (MTAP WT) cells. TNG908 shows selective antitumor activity when dosed orally in mouse xenograft models, and its physicochemical properties are amenable for crossing the blood-brain barrier (BBB), supporting clinical study for the treatment of both CNS and non-CNS tumors with MTAP loss. | ||
| - | + | Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP-Deleted Cancers.,Cottrell KM, Briggs KJ, Whittington DA, Jahic H, Ali JA, Davis CB, Gong S, Gotur D, Gu L, McCarren P, Tonini MR, Tsai A, Wilker EW, Yuan H, Zhang M, Zhang W, Huang A, Maxwell JP J Med Chem. 2024 Apr 25;67(8):6064-6080. doi: 10.1021/acs.jmedchem.4c00133. Epub , 2024 Apr 10. PMID:38595098<ref>PMID:38595098</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Whittington | + | <div class="pdbe-citations 8vew" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Whittington DA]] | ||
Current revision
Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 24
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