Epigenetic Drug Discovery: Targeting DNA Methyltransferases
| Autor: | Michael V. McCullar, K. Mark Parnell, Suzanna Chau, Steven B. Kanner, Kevin Wright, Rebecca N. Nix, Michael Saunders, Hendrickson Thomas, Jason M. Foulks, Koc-Kan Ho, K. Swierczek |
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| Rok vydání: | 2012 |
| Předmět: |
Methyltransferase
Decitabine Antineoplastic Agents Biology Biochemistry Epigenesis Genetic Analytical Chemistry Neoplasms Drug Discovery medicine Humans Epigenetics Enzyme Inhibitors DNA Modification Methylases Genetics Oligonucleotide Drug discovery Methylation DNA Methylation CpG site DNA methylation Azacitidine Cancer research Molecular Medicine Biotechnology medicine.drug |
| Zdroj: | SLAS Discovery. 17:2-17 |
| ISSN: | 2472-5552 |
| Popis: | Epigenetic modification of DNA leads to changes in gene expression. DNA methyltransferases (DNMTs) comprise a family of nuclear enzymes that catalyze the methylation of CpG dinucleotides, resulting in an epigenetic methylome distinguished between normal cells and those in disease states such as cancer. Disrupting gene expression patterns through promoter methylation has been implicated in many malignancies and supports DNMTs as attractive therapeutic targets. This review focuses on the rationale of targeting DNMTs in cancer, the historical approach to DNMT inhibition, and current marketed hypomethylating therapeutics azacytidine and decitabine. In addition, we address novel DNMT inhibitory agents emerging in development, including CP-4200 and SGI-110, analogs of azacytidine and decitabine, respectively; the oligonucleotides MG98 and miR29a; and a number of reversible inhibitors, some of which appear to be selective against particular DNMT isoforms. Finally, we discuss future opportunities and challenges for next-generation therapeutics. |
| Databáze: | OpenAIRE |
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