View source for 7buc


==Crystal structure of EHMT2 SET domain in complex with compound 13==
<StructureSection load='7buc' size='340' side='right'caption='[[7buc]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== 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 [https://proteopedia.org/fgij/fg.htm?mol=7BUC 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]] 2.6&#8491;</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>
<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&reg;/PubMed&reg;, 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__
</StructureSection>
[[Category: Large Structures]]
[[Category: Katayama K]]
[[Category: Mizuno M]]
[[Category: Suzuki M]]