6h9b
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==1,1-Diheterocyclic Ethylenes Derived from Quinaldine and Carbazole as New Tubulin Polymerization Inhibitors: Synthesis, Metabolism, and Biological Evaluation== | |
| + | <StructureSection load='6h9b' size='340' side='right' caption='[[6h9b]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6h9b]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H9B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H9B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FWH:9-methyl-3-[1-(2-methylquinolin-4-yl)ethenyl]carbazole'>FWH</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6h9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h9b OCA], [http://pdbe.org/6h9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h9b RCSB], [http://www.ebi.ac.uk/pdbsum/6h9b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h9b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the synthesis, metabolism and biological evaluation of a series of 17 novel heterocyclic derivatives of isoCombretastatin-A4 and their structure-activity relationship. Among these derivatives, the most active compound 4f inhibited the growth of a panel of seven cancer cell lines with an IC50 in the low nanomolar range. In addition, 4f showed interesting activity against CA-4-resistant colon carcinoma cells and multidrug-resistant leukemia cells. It also induced G2/M cell cycle arrest. Structural data indicated binding of 4f to the colchicine site of tubulin, likely preventing the curved-to-straight tubulin structural changes that occur during microtubule assembly. Also, 4f disrupted the blood vessel-like assembly formed by human umbilical vein endothelial cells in vitro, suggesting its function as vascular disrupting agent. In vitro metabolism study of 4f showed its high human microsomal stability in comparison to isoCA-4. The physicochemical properties of 4f may be conducive to CNS permeability suggesting that this compound may be a possible candidate for the treatment of glioblastoma. | ||
| - | + | 1,1-Diheterocyclic Ethylenes Derived from Quinaldine and Carbazole as New Tubulin Polymerization Inhibitors: Synthesis, Metabolism, and Biological Evaluation.,Naret T, Khelifi I, Provot O, Bignon J, Levaique H, Dubois J, Souce M, Kasselouri A, Deroussent A, Paci A, Varela PF, Gigant B, Alami M, Hamze A J Med Chem. 2018 Dec 10. doi: 10.1021/acs.jmedchem.8b01386. PMID:30525602<ref>PMID:30525602</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6h9b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Ovis aries]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Gigant, B]] | ||
| + | [[Category: Varela, P F]] | ||
| + | [[Category: Cell division]] | ||
| + | [[Category: Cytoskeleton]] | ||
| + | [[Category: Intracellular transport]] | ||
| + | [[Category: Transport protein]] | ||
Revision as of 08:29, 19 December 2018
1,1-Diheterocyclic Ethylenes Derived from Quinaldine and Carbazole as New Tubulin Polymerization Inhibitors: Synthesis, Metabolism, and Biological Evaluation
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