Non-isotopic dual parameter competition assay suitable for high-throughput screening of histone deacetylases

Histone deacetylases reside among the most important and novel target classes in oncology. Selective lead structures are intensively developed to improve efficacy and reduce adverse effects. The common assays used so far to identify new lead structures suffer from many false positive hits due to aut...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-07, Vol.19 (13), p.3651-3656
Main Authors: Riester, Daniel, Hildmann, Christian, Haus, Patricia, Galetovic, Antonia, Schober, Andreas, Schwienhorst, Andreas, Meyer-Almes, Franz-Josef
Format: Article
Language:English
Subjects:
Biological and medical sciences
Competition assay
Drug Evaluation, Preclinical
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - metabolism
Enzyme Inhibitors - pharmacology
Fluorescence Resonance Energy Transfer
Fluorescent Dyes - chemistry
Fluorogenic substrates
FRET
High-throughput screening assay
Histone deacetylase
Histone Deacetylase Inhibitors
Histone Deacetylases - metabolism
Medical sciences
Miscellaneous
Pharmacology. Drug treatments
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Summary:Histone deacetylases reside among the most important and novel target classes in oncology. Selective lead structures are intensively developed to improve efficacy and reduce adverse effects. The common assays used so far to identify new lead structures suffer from many false positive hits due to auto-fluorescence of compounds or triggering undesired signal transduction pathways. These drawbacks are eliminated by the dual parameter competition assay reported in this study. The assay involves a new fluorescent inhibitor probe that shows an increase in both, fluorescence anisotropy and fluorescence lifetime upon binding to the enzyme. The assay is well suited for high-throughput screening.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.04.102