8u8x
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==crystal structure of the receptor tyrosine kinase Human HER2 (ERBB2) YVMA mutant kinase domain in complex with inhibitor compound 27== | |
| + | <StructureSection load='8u8x' size='340' side='right'caption='[[8u8x]], [[Resolution|resolution]] 1.69Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8u8x]] 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=8U8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8U8X 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]] 1.69Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=W9N:1-{(1R,3r,5S)-3-[(3M)-4-methyl-3-{3-methyl-4-[(1-methyl-1H-benzimidazol-5-yl)oxy]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-8-azabicyclo[3.2.1]octan-8-yl}propan-1-one'>W9N</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=8u8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8u8x OCA], [https://pdbe.org/8u8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8u8x RCSB], [https://www.ebi.ac.uk/pdbsum/8u8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8u8x ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | HER2 overexpression and amplification have been identified as oncogenic drivers, and the development of therapies to treat tumors harboring these markers has received considerable attention. Activation of HER2 signaling and subsequent cell growth can also be induced by HER2 mutations, including the common YVMA insertion in exon 20 within the kinase domain. Enhertu is currently the only approved treatment for HER2 mutant tumors in NSCLC. TKIs tested in this space have suffered from off-target activity, primarily due to EGFR(WT) inhibition or attenuated activity against HER2 mutants. The goal of this work was to identify a TKI that would provide robust inhibition of oncogenic HER2(WT) and HER2 mutants while sparing EGFR(WT) activity. Herein, we describe the development of a potent, covalent inhibitor of HER2(WT) and the YVMA insertion mutant while providing oral bioavailability and avoiding the inhibition of EGFR(WT). | ||
| - | + | Discovery of Potent and Selective Covalent Inhibitors of HER2(WT) and HER2(YVMA).,Hicken EJ, Brown K, Dwulet NC, Gaudino JJ, Hansen EP, Hartley DP, Kowalski JP, Laird ER, Lazzara NC, Li B, Mou TC, Mutryn MF, Oko L, Pajk S, Pipal RW, Rosen RZ, Shelp R, Singh A, Wang J, Wise CE, Wong C, Wong JY J Med Chem. 2024 May 31. doi: 10.1021/acs.jmedchem.4c00978. PMID:38820338<ref>PMID:38820338</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Mou | + | <div class="pdbe-citations 8u8x" style="background-color:#fffaf0;"></div> |
| - | [[Category: Wang | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mou TC]] | ||
| + | [[Category: Wang J]] | ||
Current revision
crystal structure of the receptor tyrosine kinase Human HER2 (ERBB2) YVMA mutant kinase domain in complex with inhibitor compound 27
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