Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling Journal Article
| Authors: | Ganesh, T.; Min, J.; Thepchatri, P.; Du, Y. H.; Li, L.; Lewis, I.; Wilson, L.; Fu, H. A.; Chiosis, G.; Dingledine, R.; Liotta, D.; Snyder, J. P.; Sun, A. M. |
| Article Title: | Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling |
| Abstract: | 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. Published by Elsevier Ltd. |
| Keywords: | assay; in-vitro; geldanamycin; radicicol; chaperone; identification; analogs; crystal-structure; target; atpase activity; heat shock protein 90 (hsp90); high-throughput screening (hts); aminoquinoline |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 16 |
| Issue: | 14 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2008-07-01 |
| Start Page: | 6903 |
| End Page: | 6910 |
| Language: | English |
| ACCESSION: | WOS:000257829600029 |
| DOI: | 10.1016/j.bmc.2008.05.047 |
| PROVIDER: | wos |
| PMCID: | PMC2553564 |
| PUBMED: | 18571929 |
| Notes: | --- - Article - "Source: Wos" |
