View source for 6wnh


==Menin bound to inhibitor M-808==
<StructureSection load='6wnh' size='340' side='right'caption='[[6wnh]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WNH 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MM:methyl+[(1S,2R)-2-{(1S)-2-(azetidin-1-yl)-1-(3-fluorophenyl)-1-[1-({1-[4-({1-[4-(piperidin-1-yl)butanoyl]azetidin-3-yl}sulfonyl)phenyl]azetidin-3-yl}methyl)piperidin-4-yl]ethyl}cyclopentyl]carbamate'>7MM</scene>, <scene name='pdbligand=7PR:praseodymium+triacetate'>7PR</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=6wnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wnh OCA], [https://pdbe.org/6wnh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wnh RCSB], [https://www.ebi.ac.uk/pdbsum/6wnh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wnh ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Targeting the menin-MLL protein-protein interaction is a new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein the structure-based optimization of a class of covalent menin inhibitors, which led to the discovery of M-808 (16) as a highly potent and efficacious covalent menin inhibitor. M-808 effectively inhibits leukemia cell growth at low nanomolar concentrations and is capable of achieving partial tumor regression in an MV4;11 xenograft tumor model in mice at a well-tolerated dose schedule. Determination of the co-crystal structure of M-808 in complex with menin provides a structural basis for their high-affinity, covalent interactions. M-808 represents a promising, covalent menin inhibitor for further optimization and evaluation toward developing a new therapy for the treatment of MLL leukemia.

Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction with Strong In Vivo Antitumor Activity.,Xu S, Aguilar A, Huang L, Xu T, Zheng K, McEachern D, Przybranowski S, Foster C, Zawacki K, Liu Z, Chinnaswamy K, Stuckey J, Wang S J Med Chem. 2020 Apr 27. doi: 10.1021/acs.jmedchem.0c00547. PMID:32338903<ref>PMID:32338903</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wnh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Menin|Menin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Stuckey JA]]