402725-52-4Relevant academic research and scientific papers
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70
Cheeseman, Matthew D.,Westwood, Isaac M.,Barbeau, Olivier,Rowlands, Martin,Dobson, Sarah,Jones, Alan M.,Jeganathan, Fiona,Burke, Rosemary,Kadi, Nadia,Workman, Paul,Collins, Ian,Van Montfort, Rob L. M.,Jones, Keith
, p. 4625 - 4636 (2016)
HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.
Anti-HCV nucleoside derivatives
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, (2008/06/13)
The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
