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A Bioluminescent HDAC Assay for Cell-Based Drug Discovery Poster

Part # PS117

Abstract

Andrew L. Niles1, Nathan Evans1 and Thomas A. Kirkland2
1Promega Corporation, Madison, WI
2Promega Biosciences L.L.C., San Luis Obispo, CA

Cell-based models continue to be an important tool in the drug discovery and development toolbox because they provide a more biologically relevant context to study the complex changes occurring after targeted intervention. Histonedeacetylase (HDAC) enzymes are an emerging group of epigenetic modifiers that are of particular interest for targeted intervention because they are well-validated and chemically tractable. We have developed a bioluminescent, single addition, homogeneous deacetylase assay that is sufficiently sensitive and robust for cell-based screening or characterization efforts in either non-lytic or lytic formats. Here we describe efforts to define the utility of the assay using structurally diverse HDAC inhibitors with both attachment-dependent and suspension cell lines. Furthermore, HDAC inhibition will be correlated with cellular fate by various multiplexed viability and cytotoxicity measures in the same well.

Printed in USA.