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 approximately 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 microM. The structures of several of these inhibitory scaffolds are reported along with their IC50 values.
Avila
Christopher
C
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7563, USA.
Hadden
M Kyle
MK
Ma
Zeqiang
Z
Kornilayev
Boris A
BA
Ye
Qi-Zhuang
QZ
Blagg
Brian S J
BS
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015394:Molecular Structure
D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D000251:Adenosine Triphosphatases