Screening for histone deacetylase (HDAC) active compounds

Franka Maurer (1), Sheraz Gul (2), Gesa Will (2) (1) BMG LABTECH, (2) European ScreeningPort GmbH 12/2013

Histones are proteins around which the DNA is wound to provide compaction. Their interaction with DNA, neighboring histones and transcription factors is highly regulated by acetylation. Deacetylation of histones is accomplished by histone deacetylases (HDACs) which are targeted for therapy of neurological diseases and cancer. Here we present the suitability of the HDAC-Glo™ I/II assay read on the PHERAstar® FS to screen for HDAC-active compounds.

The HDAC-Glo I/II assay uses a substrate that upon deacetylation by HDACs is prone to be cleaved by a protease resulting in a luciferase substrate. Addition of the luciferase gives a luminescence signal proportional to the HDAC activity.

This assay allowed for determination of the IC50 value of TSA, a well-known HDAC inhibitor. Furthermore, a compound library was screened and revealed HDAC inhibitory activity of substances. False negatives were successfully revealed by running a counterscreen with the deacetylated substrate.

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