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3rkz

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Revision as of 09:24, 5 August 2016

Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor capable of significantly decreasing tumor volume in a mouse xenograft model.

Structural highlights

3rkz is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	HSP90A, HSP90AA1, HSPC1, HSPCA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.^[1] ^[2]

Publication Abstract from PubMed

An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction.

Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model.,Zapf CW, Bloom JD, Li Z, Dushin RG, Nittoli T, Otteng M, Nikitenko A, Golas JM, Liu H, Lucas J, Boschelli F, Vogan E, Olland A, Johnson M, Levin JI Bioorg Med Chem Lett. 2011 Jun 27. PMID:21715165^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
↑ Zapf CW, Bloom JD, Li Z, Dushin RG, Nittoli T, Otteng M, Nikitenko A, Golas JM, Liu H, Lucas J, Boschelli F, Vogan E, Olland A, Johnson M, Levin JI. Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model. Bioorg Med Chem Lett. 2011 Jun 27. PMID:21715165 doi:10.1016/j.bmcl.2011.05.102

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3rkz"

@@ Line 1: / Line 1: @@
 ==Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor capable of significantly decreasing tumor volume in a mouse xenograft model.==
 <StructureSection load='3rkz' size='340' side='right' caption='[[3rkz]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rkz]] 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=3RKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RKZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rkz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RKZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06T:(5R,6S)-3-(L-ALANYL)-5,6,15,15,18-PENTAMETHYL-17-OXO-2,3,4,5,6,7,14,15,16,17-DECAHYDRO-1H-12,8-(METHENO)[1,5,9]TRIAZACYCLOTETRADECINO[1,2-A]INDOLE-9-CARBOXAMIDE'>06T</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='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 HUMAN])</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=3rkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rkz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rkz RCSB], [http://www.ebi.ac.uk/pdbsum/3rkz PDBsum]</span></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=3rkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rkz OCA], [http://pdbe.org/3rkz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rkz RCSB], [http://www.ebi.ac.uk/pdbsum/3rkz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rkz ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3rkz" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Bloom, J D]]
 [[Category: Boschelli, F]]

3rkz

From Proteopedia

Revision as of 09:24, 5 August 2016

Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor capable of significantly decreasing tumor volume in a mouse xenograft model.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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