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==Hsp90 alpha N-terminal domain in complex with an inhibitor CH4675194== | |||
<StructureSection load='3b25' size='340' side='right' caption='[[3b25]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3b25]] 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=3B25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B25 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B2K:4-METHYL-6-(TOLUENE-4-SULFONYL)-PYRIMIDIN-2-YLAMINE'>B2K</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3b24|3b24]], [[3b26|3b26]], [[3b27|3b27]], [[3b28|3b28]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1 ([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=3b25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b25 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3b25 RCSB], [http://www.ebi.ac.uk/pdbsum/3b25 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models. | |||
Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design.,Miura T, Fukami TA, Hasegawa K, Ono N, Suda A, Shindo H, Yoon DO, Kim SJ, Na YJ, Aoki Y, Shimma N, Tsukuda T, Shiratori Y Bioorg Med Chem Lett. 2011 Oct 1;21(19):5778-83. Epub 2011 Aug 6. PMID:21875802<ref>PMID:21875802</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Heat Shock Proteins|Heat Shock Proteins]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Fukami, T A | [[Category: Fukami, T A]] | ||
[[Category: Ono, N | [[Category: Ono, N]] | ||
[[Category: Chaperone-chaperone inhibitor complex]] | [[Category: Chaperone-chaperone inhibitor complex]] | ||
Revision as of 17:23, 18 December 2014
Hsp90 alpha N-terminal domain in complex with an inhibitor CH4675194Hsp90 alpha N-terminal domain in complex with an inhibitor CH4675194
Structural highlights
Publication Abstract from PubMedHeat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models. Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design.,Miura T, Fukami TA, Hasegawa K, Ono N, Suda A, Shindo H, Yoon DO, Kim SJ, Na YJ, Aoki Y, Shimma N, Tsukuda T, Shiratori Y Bioorg Med Chem Lett. 2011 Oct 1;21(19):5778-83. Epub 2011 Aug 6. PMID:21875802[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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