2. Academic Validation
  3. Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling

Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling

  • Bioorg Med Chem. 2008 Jul 15;16(14):6903-10. doi: 10.1016/j.bmc.2008.05.047.
Thota Ganesh 1,  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
Affiliations

Affiliation

  • 1 Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA.
PMID: 18571929 DOI: 10.1016/j.bmc.2008.05.047
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.

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