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3r91

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Revision as of 05:21, 25 December 2014

Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.

Structural highlights

3r91 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	HSP90A, HSP90AA1, HSPC1, HSPCA (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24h post-administration, consistent with elevated and prolonged exposure in the tumor.

Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.,Zapf CW, Bloom JD, McBean JL, Dushin RG, Nittoli T, Otteng M, Ingalls C, Golas JM, Liu H, Lucas J, Boschelli F, Hu Y, Vogan E, Levin JI Bioorg Med Chem Lett. 2011 Apr 5. PMID:21515049^[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, McBean JL, Dushin RG, Nittoli T, Otteng M, Ingalls C, Golas JM, Liu H, Lucas J, Boschelli F, Hu Y, Vogan E, Levin JI. Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity. Bioorg Med Chem Lett. 2011 Apr 5. PMID:21515049 doi:10.1016/j.bmcl.2011.03.112

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/3r91"

@@ Line 7: / Line 7: @@
 <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=3r91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r91 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r91 RCSB], [http://www.ebi.ac.uk/pdbsum/3r91 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HS90A_HUMAN 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.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3r91

From Proteopedia

Revision as of 05:21, 25 December 2014

Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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