High-throughput screening for Hsp90 ATPase inhibitors

Christopher Avila; M Kyle Hadden; Zeqiang Ma; Boris A Kornilayev; Qi-Zhuang Ye; Brian S J Blagg

doi:10.1016/j.bmcl.2006.02.063

High-throughput screening for Hsp90 ATPase inhibitors

Bioorg Med Chem Lett. 2006 Jun 1;16(11):3005-8. doi: 10.1016/j.bmcl.2006.02.063. Epub 2006 Mar 10.

Authors

Christopher Avila¹, M Kyle Hadden, Zeqiang Ma, Boris A Kornilayev, Qi-Zhuang Ye, Brian S J Blagg

Affiliation

¹ Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7563, USA.

PMID: 16530412
DOI: 10.1016/j.bmcl.2006.02.063

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / antagonists & inhibitors*
Adenosine Triphosphatases / metabolism*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
HSP90 Heat-Shock Proteins / antagonists & inhibitors*
HSP90 Heat-Shock Proteins / metabolism*
Molecular Structure

Substances

Enzyme Inhibitors
HSP90 Heat-Shock Proteins
Adenosine Triphosphatases

Abstract

Publication types

MeSH terms

Substances

Grants and funding