6bxy
From Proteopedia
(Difference between revisions)
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==Menin in complex with MI-1481== | ==Menin in complex with MI-1481== | ||
| - | <StructureSection load='6bxy' size='340' side='right' caption='[[6bxy]], [[Resolution|resolution]] 1.82Å' scene=''> | + | <StructureSection load='6bxy' size='340' side='right'caption='[[6bxy]], [[Resolution|resolution]] 1.82Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6bxy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BXY FirstGlance]. <br> | <table><tr><td colspan='2'>[[6bxy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BXY FirstGlance]. <br> | ||
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxy OCA], [http://pdbe.org/6bxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bxy RCSB], [http://www.ebi.ac.uk/pdbsum/6bxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxy ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxy OCA], [http://pdbe.org/6bxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bxy RCSB], [http://www.ebi.ac.uk/pdbsum/6bxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The protein-protein interaction between menin and mixed-lineage leukemia 1 (MLL1) plays an important role in development of acute leukemia with translocations of the MLL1 gene and in solid tumors. Here, we report the development of a new generation of menin-MLL1 inhibitors identified by structure-based optimization of the thienopyrimidine class of compounds. This work resulted in compound 28 (MI-1481), which showed very potent inhibition of the menin-MLL1 interaction (IC50 = 3.6 nM), representing the most potent reversible menin-MLL1 inhibitor reported to date. The crystal structure of the menin-28 complex revealed a hydrogen bond with Glu366 and hydrophobic interactions, which contributed to strong inhibitory activity of 28. Compound 28 also demonstrates pronounced activity in MLL leukemia cells and in vivo in MLL leukemia models. Thus, 28 is a valuable menin-MLL1 inhibitor that can be used for potential therapeutic applications and in further studies regarding the role of menin in cancer. | ||
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| + | Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction.,Borkin D, Klossowski S, Pollock J, Miao H, Linhares BM, Kempinska K, Jin Z, Purohit T, Wen B, He M, Sun D, Cierpicki T, Grembecka J J Med Chem. 2018 Jun 14;61(11):4832-4850. doi: 10.1021/acs.jmedchem.8b00071. Epub, 2018 May 23. PMID:29738674<ref>PMID:29738674</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6bxy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Borkin, D]] | [[Category: Borkin, D]] | ||
[[Category: Cierpicki, T]] | [[Category: Cierpicki, T]] | ||
Revision as of 06:08, 12 June 2019
Menin in complex with MI-1481
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