Structural ensemble-based docking simulation and biophysical studies discovered new inhibitors of Hsp90 N-terminal domain.

ABSTRACT: Heat shock protein 90 (Hsp90) is one of the most abundant cellular proteins and plays a substantial role in the folding of client proteins. The inhibition of Hsp90 has been regarded as an attractive therapeutic strategy for treating cancer because many oncogenic kinases are Hsp90 client proteins. In this study, we report new inhibitors that directly bind to N-terminal ATP-binding pocket of Hsp90. Optimized structure-based virtual screening predicted candidate molecules, which was followed by confirmation using biophysical and cell-based assays. Among the reported crystal structures, we chose the two structures that show the most favourable early enrichments of true-positives in the receiver operating characteristic curve. Four molecules showed significant changes in the signals of 2D [

SUBMITTER: Kim HH 

PROVIDER: S-EPMC5762686 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature