Identification of Four Potential Epigenetic Modulators from the NCI Structural Diversity Library Using a Cell-Based Assay
| Autor: | John A. Beutler, Jianjun Chang, Anne M. Best, Angie B. Dull, Elisabeth D. Martinez |
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| Rok vydání: | 2011 |
| Předmět: |
Article Subject
Transcription Genetic lcsh:Biotechnology Health Toxicology and Mutagenesis Green Fluorescent Proteins lcsh:Medicine Antineoplastic Agents Mice Transgenic Biology Epigenesis Genetic Small Molecule Libraries Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms lcsh:TP248.13-248.65 Genetics Animals Humans Gene silencing Cancer epigenetics Epigenetics Molecular Biology Gene 030304 developmental biology 0303 health sciences Drug discovery lcsh:R General Medicine National Cancer Institute (U.S.) United States 3. Good health Cell biology Histone Acetylation 030220 oncology & carcinogenesis biology.protein Molecular Medicine Biological Assay Histone deacetylase activity Drug Screening Assays Antitumor Research Article Biotechnology |
| Zdroj: | Journal of Biomedicine and Biotechnology, Vol 2011 (2011) Journal of Biomedicine and Biotechnology |
| ISSN: | 1110-7251 1110-7243 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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