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6ud2
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==co-crystal structure of compound 1 bound to human Mcl-1== | |
| + | <StructureSection load='6ud2' size='340' side='right'caption='[[6ud2]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ud2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UD2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UD2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q4D:(4S,7aR,9aR,10S,11E,18R)-6-chloro-10-[2-(3,3-difluoroazetidin-1-yl)ethoxy]-N-(dimethylsulfamoyl)-18-hydroxy-15-methyl-16-oxo-3,4,7,7a,8,9,9a,10,13,14,15,16,17,18-tetradecahydro-2H,3H,5H-spiro[1,19-(ethanediylidene)cyclobuta[n][1,4]oxazepino[4,3-a][1,8]diazacyclohexadecine-4,1-naphthalene]-18-carboxamide'>Q4D</scene></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=6ud2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ud2 OCA], [http://pdbe.org/6ud2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ud2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ud2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ud2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN]] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an alpha-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of 1, a potent Mcl-1 inhibitor (IC50 = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model. | ||
| - | + | Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an alpha-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere.,Rescourio G, Gonzalez AZ, Jabri S, Belmontes B, Moody G, Whittington D, Huang X, Caenepeel S, Cardozo M, Cheng AC, Chow D, Dou H, Jones A, Kelly RC, Li Y, Lizarzaburu M, Lo MC, Mallari R, Meleza C, Rew Y, Simonovich S, Sun D, Turcotte S, Yan X, Wong SG, Yanez E, Zancanella M, Houze J, Medina JC, Hughes PE, Brown SP J Med Chem. 2019 Nov 27;62(22):10258-10271. doi: 10.1021/acs.jmedchem.9b01310., Epub 2019 Nov 18. PMID:31736296<ref>PMID:31736296</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6ud2" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Huang, X]] | [[Category: Huang, X]] | ||
| + | [[Category: Whittington, D]] | ||
| + | [[Category: Apoptosis]] | ||
| + | [[Category: Apoptosis-inhibitor complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Protein-protein interaction]] | ||
Revision as of 08:21, 4 December 2019
co-crystal structure of compound 1 bound to human Mcl-1
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