3r92
From Proteopedia
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| - | [[ | + | ==Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model.== |
| + | <StructureSection load='3r92' size='340' side='right' caption='[[3r92]], [[Resolution|resolution]] 1.58Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3r92]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R92 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06J:(3AR)-13,13,16-TRIMETHYL-15-OXO-1,2,3,3A,4,5,12,14,15,17,18,19-DODECAHYDRO-13H-10,6-(METHENO)PYRROLO[2,1 3,4][1,4,9]TRIAZACYCLOTETRADECINO[9,8-A]INDOLE-7-CARBOXAMIDE'>06J</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90A, HSP90AA1, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3r92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r92 RCSB], [http://www.ebi.ac.uk/pdbsum/3r92 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research, heterocycle-containing tethers were explored with the intent to further improve potency and minimize hERG liabilities. This effort culminated in the discovery of compound 10, which efficiently suppressed proliferation of HCT116 and U87 cells. This compound showed prolonged Hsp90-inhibitory activity at least 24h post-administration consistent with elevated and prolonged exposure in the tumor. When studied in a xenograft model, the compound demonstrated significant suppression of tumor growth. | ||
| - | + | Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model.,Zapf CW, Bloom JD, McBean JL, Dushin RG, Golas JM, Liu H, Lucas J, Boschelli F, Vogan E, Levin JI Bioorg Med Chem Lett. 2011 Jun 15;21(12):3627-31. Epub 2011 Apr 28. PMID:21605975<ref>PMID:21605975</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Heat Shock Proteins|Heat Shock Proteins]] | *[[Heat Shock Proteins|Heat Shock Proteins]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Bloom, J D | + | [[Category: Bloom, J D]] |
| - | [[Category: Boschelli, F | + | [[Category: Boschelli, F]] |
| - | [[Category: Dushin, R G | + | [[Category: Dushin, R G]] |
| - | [[Category: Golas, J M | + | [[Category: Golas, J M]] |
| - | [[Category: Levin, J I | + | [[Category: Levin, J I]] |
| - | [[Category: Liu, H | + | [[Category: Liu, H]] |
| - | [[Category: Lucas, J | + | [[Category: Lucas, J]] |
| - | [[Category: McBean, J L | + | [[Category: McBean, J L]] |
| - | [[Category: Vogan, E M | + | [[Category: Vogan, E M]] |
| - | [[Category: Zapf, C W | + | [[Category: Zapf, C W]] |
[[Category: Atp binding domain]] | [[Category: Atp binding domain]] | ||
[[Category: Atp-binding]] | [[Category: Atp-binding]] | ||
Revision as of 10:48, 9 December 2014
Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model.
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