7buc
From Proteopedia
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==Crystal structure of EHMT2 SET domain in complex with compound 13== | ==Crystal structure of EHMT2 SET domain in complex with compound 13== | ||
| - | <StructureSection load='7buc' size='340' side='right'caption='[[7buc]]' scene=''> | + | <StructureSection load='7buc' size='340' side='right'caption='[[7buc]], [[Resolution|resolution]] 2.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BUC OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F80:N2-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-N4,6-dimethyl-pyrimidine-2,4-diamine'>F80</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [https://pdbe.org/7buc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [https://www.ebi.ac.uk/pdbsum/7buc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors. | ||
| + | |||
| + | Discovery of novel histone lysine methyltransferase G9a/GLP (EHMT2/1) inhibitors: Design, synthesis, and structure-activity relationships of 2,4-diamino-6-methylpyrimidines.,Katayama K, Ishii K, Tsuda E, Yotsumoto K, Hiramoto K, Suzuki M, Yasumatsu I, Igarashi W, Torihata M, Ishiyama T, Katagiri T Bioorg Med Chem Lett. 2020 Oct 15;30(20):127475. doi: 10.1016/j.bmcl.2020.127475., Epub 2020 Aug 8. PMID:32781218<ref>PMID:32781218</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7buc" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of EHMT2 SET domain in complex with compound 13
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