Document Detail

Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling.
MedLine Citation:
PMID:  18571929     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-05-27
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  16     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-25     Completed Date:  2008-09-11     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6903-10     Citation Subset:  IM    
Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA.
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MeSH Terms
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
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
Reg. No./Substance:
0/Aminoquinolines; 0/Antineoplastic Agents; 0/HSP90 Heat-Shock Proteins

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