Identification of four potential epigenetic modulators from the NCI structural diversity library using a cell-based assay

Elisabeth D. Martinez, Anne M. Best, Jianjun Chang, Angie B. Dull, John A. Beutler

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number868095
JournalJournal of Biomedicine and Biotechnology
Volume2011
DOIs
StatePublished - 2011

Fingerprint

Epigenomics
Modulators
Libraries
Assays
Genes
Histones
Acetylation
Histone Deacetylases
Chemical modification
Cell growth
Enzymes
Drug Discovery
Machinery
Melanoma
Lung Neoplasms
Cell Cycle
Fluorescence
Cells
Gene Expression
Imaging techniques

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Identification of four potential epigenetic modulators from the NCI structural diversity library using a cell-based assay. / Martinez, Elisabeth D.; Best, Anne M.; Chang, Jianjun; Dull, Angie B.; Beutler, John A.

In: Journal of Biomedicine and Biotechnology, Vol. 2011, 868095, 2011.

Research output: Contribution to journalArticle

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