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A Multiplexed Bioluminescent HDAC Assay for Target-Specific Anti-Cancer Potency...

A Multiplexed Bioluminescent HDAC Assay for Target-Specific Anti-Cancer Potency Scientific Poster

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Abstract

Nathan J. Evans1, Thomas A. Kirkland2, and Andrew L. Niles1
1Promega Corporation, 2800 Woods Hollow Rd., Madison, WI, 53711
2Promega Biosciences LLC., 277 Granada Dr., San Luis Obispo, CA, 93401 
AACR 2011 Abstract# 3028

Histone deacetylase (HDAC) class I and II enzymes are zinc dependent protein deacetylases. They play many roles in normal gene regulation events of development and homeostasis, but their dysregulation has been linked to a variety of solid tumors and hematological malignancies. We have recently developed a one-step, homogeneous, luminescent assay for activity detection from multiple HDAC Class I and II isoforms, thereby providing a useful tool for cell culture, enriched or recombinant sources of lysine deacetylases. This luciferase-containing, “glow-type” assay reagent is cell-permeable and can directly measure HDAC activity in living attachment-dependent and suspension cells. Furthermore, this luminescent HDAC assay can be paired in same well multiplex formats with fluorescent assays which measure biomarkers associated with changes in viability and cytotoxicity. Here we correlate HDAC inhibition with cellular fate, using representative inhibitors from the hydroxamate, short-chain fatty acid, benzamide and cyclic peptide classes. We will also demonstrate relative on-target anti-cancer efficacies and off-target safety using transformed, primary or iPS-derived cell lineages.

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  • Part# PS127
  • Printed in USA.

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