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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 868095, 11 pages
Research Article

Identification of Four Potential Epigenetic Modulators from the NCI Structural Diversity Library Using a Cell-Based Assay

1Department of Pharmacology and Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
2Molecular Targets Laboratory, Center for SAIC-Frederick, National Cancer Institute, Frederick, MD 21702, USA
3Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Boulevard, Dallas, TX 75390, USA

Received 29 July 2010; Accepted 7 October 2010

Academic Editor: Minoru Yoshida

Copyright © 2011 Anne M. Best et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Epigenetic pathways help control the expression of genes. In cancer and other diseases, aberrant silencing or overexpression of genes, such as those that control cell growth, can greatly contribute to pathogenesis. Access to these genes by the transcriptional machinery is largely mediated by chemical modifications of DNA or histones, which are controlled by epigenetic enzymes, making these enzymes attractive targets for drug discovery. Here we describe the characterization of a locus derepression assay, a fluorescence-based mammalian cellular system which was used to screen the NCI structural diversity library for novel epigenetic modulators using an automated imaging platform. Four structurally unique compounds were uncovered that, when further investigated, showed distinct activities. These compounds block the viability of lung cancer and melanoma cells, prevent cell cycle progression, and/or inhibit histone deacetylase activity, altering levels of cellular histone acetylation.