| Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling. | |
MedLine Citation:
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PMID: 18571929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The molecular chaperone Hsp90 plays important roles in maintaining malignant phenotypes. Recent studies suggest that Hsp90 exerts high-affinity interactions with multiple oncoproteins, which are essential for the growth of tumor cells. As a result, research has focused on finding Hsp90 probes as potential and selective anticancer agents. In a high-throughput screening exercise, we identified quinoline 7 as a moderate inhibitor of Hsp90. Further hit identification, SAR studies, and biological investigation revealed several synthetic analogs in this series with micromolar activities in both fluorescent polarization (FP) assay and a cell-based Western blot (WB) assay. These compounds represent a new class of Hsp90 inhibitors with simple chemical structures. |
Authors:
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Thota Ganesh; Jaeki Min; Pahk Thepchatri; Yuhong Du; Lian Li; Iestyn Lewis; Larry Wilson; Haian Fu; Gabriela Chiosis; Raymond Dingledine; Dennis Liotta; James P Snyder; Aiming Sun |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-05-27 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 16 ISSN: 1464-3391 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-07-25 Completed Date: 2008-09-11 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 6903-10 Citation Subset: IM |
Affiliation:
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Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminoquinolines
/
chemical synthesis,
chemistry,
pharmacology* Antineoplastic Agents Blotting, Western Drug Evaluation, Preclinical Fluorescence Polarization Immunoassay HSP90 Heat-Shock Proteins / antagonists & inhibitors* Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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1 U54 HG003918-02/HG/NHGRI NIH HHS; 1R03MH076499-01/MH/NIMH NIH HHS; U54 HG003918/HG/NHGRI NIH HHS; U54 HG003918-02/HG/NHGRI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aminoquinolines; 0/Antineoplastic Agents; 0/HSP90 Heat-Shock Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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