High-throughput screening for Hsp90 ATPase inhibitors

Recently, we reported a useful assay for the determination of yeast Hsp90 ATPase activity. Using this assay, high-throughput screening of ∼10,000 compounds was performed to determine the feasibility of this assay on large scale. Results from high-throughput screening indicated that the assay was reproducible (av Z-factor = 0.80) and identified 0.57% of the compounds as Hsp90 inhibitors that exhibited IC50s less than 20 μM. The structures of several of these inhibitory scaffolds are reported along with their IC50 values.

Graphical abstractRecently, we reported a useful assay for the determination of Hsp90 ATPase activity. Using this assay, high-throughput screening of ∼10,000 compounds was performed to determine the feasibility of this assay on large scale. Results from high-throughput screening indicated that the assay was reproducible (av Z-factor = 0.80) and identified 0.57% of the compounds as Hsp90 inhibitors that exhibited IC50s less than 20 μM. The structures of several of these inhibitory scaffolds are reported along with their IC50 values.Figure optionsDownload full-size imageDownload as PowerPoint slide