4awo: Difference between revisions

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-[[Image:4awo.jpg|left|200px]]
+==Complex of HSP90 ATPase domain with tropane derived inhibitors==
+<StructureSection load='4awo' size='340' side='right' caption='[[4awo]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4awo]] is a 2 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=4AWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AWO FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=99B:5-[(2R)-BUTAN-2-YLAMINO]-N-{(3-ENDO)-8-[5-(CYCLOPROPYLCARBONYL)PYRIDIN-2-YL]-8-AZABICYCLO[3.2.1]OCT-3-YL}-2-METHYLBENZENE-1,4-DICARBOXAMIDE'>99B</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1byq|1byq]], [[1osf|1osf]], [[1uy6|1uy6]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyh|1uyh]], [[1uyi|1uyi]], [[1uyk|1uyk]], [[1uyl|1uyl]], [[1yc1|1yc1]], [[1yc3|1yc3]], [[1yc4|1yc4]], [[1yer|1yer]], [[1yes|1yes]], [[1yet|1yet]], [[2bsm|2bsm]], [[2bt0|2bt0]], [[2bug|2bug]], [[2byh|2byh]], [[2byi|2byi]], [[2bz5|2bz5]], [[2c2l|2c2l]], [[2ccs|2ccs]], [[2cct|2cct]], [[2ccu|2ccu]], [[2fwy|2fwy]], [[2fwz|2fwz]], [[2jjc|2jjc]], [[2uwd|2uwd]], [[2vci|2vci]], [[2vcj|2vcj]], [[2wi1|2wi1]], [[2wi2|2wi2]], [[2wi3|2wi3]], [[2wi4|2wi4]], [[2wi5|2wi5]], [[2wi6|2wi6]], [[2wi7|2wi7]], [[2xab|2xab]], [[2xdk|2xdk]], [[2xdl|2xdl]], [[2xds|2xds]], [[2xdu|2xdu]], [[2xdx|2xdx]], [[2xhr|2xhr]], [[2xht|2xht]], [[2xhx|2xhx]], [[2xjg|2xjg]], [[2xjj|2xjj]], [[2xjx|2xjx]], [[2xk2|2xk2]], [[2ye2|2ye2]], [[2ye3|2ye3]], [[2ye4|2ye4]], [[2ye5|2ye5]], [[2ye6|2ye6]], [[2ye7|2ye7]], [[2ye8|2ye8]], [[2ye9|2ye9]], [[2yea|2yea]], [[2yeb|2yeb]], [[2yec|2yec]], [[2yed|2yed]], [[2yee|2yee]], [[2yef|2yef]], [[2yeg|2yeg]], [[2yeh|2yeh]], [[2yei|2yei]], [[2yej|2yej]], [[2yi0|2yi0]], [[2yi5|2yi5]], [[2yi6|2yi6]], [[2yi7|2yi7]], [[2yjw|2yjw]], [[2yjx|2yjx]], [[2yk2|2yk2]], [[2yk9|2yk9]], [[2ykb|2ykb]], [[2ykc|2ykc]], [[2yke|2yke]], [[2yki|2yki]], [[2ykj|2ykj]], [[4aif|4aif]], [[4awp|4awp]], [[4awq|4awq]]</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-chaperonin_molecular_chaperone_ATPase Non-chaperonin molecular chaperone ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.10 3.6.4.10] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4awo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4awo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4awo RCSB], [http://www.ebi.ac.uk/pdbsum/4awo PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens.
-{{STRUCTURE_4awo|  PDB=4awo  |  SCENE=  }}
+Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90.,Bussenius J, Blazey CM, Aay N, Anand NK, Arcalas A, Baik T, Bowles OJ, Buhr CA, Costanzo S, Curtis JK, Defina SC, Dubenko L, Heuer TS, Huang P, Jaeger C, Joshi A, Kennedy AR, Kim AI, Lara K, Lee J, Li J, Lougheed JC, Ma S, Malek S, Manalo JC, Martini JF, McGrath G, Nicoll M, Nuss JM, Pack M, Peto CJ, Tsang TH, Wang L, Womble SW, Yakes M, Zhang W, Rice KD Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. Epub 2012 Jul 21. PMID:22877636<ref>PMID:22877636</ref>
-===Complex of HSP90 ATPase domain with tropane derived inhibitors===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_22877636}}
+==See Also==
+*[[Heat Shock Proteins|Heat Shock Proteins]]
-==About this Structure==
+== References ==
-[[4awo]] is a 2 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=4AWO OCA].
+<references/>
+__TOC__
-==Reference==
+</StructureSection>
-<ref group="xtra">PMID:022877636</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
 [[Category: Non-chaperonin molecular chaperone ATPase]]