Toward Drug Repurposing in Epigenetics: Olsalazine as a Hypomethylating Compound Active in a Cellular Context
Abbreviated Journal Title
cancer; DNA methylation; drug discovery; drug repurposing; hypomethylating agents; similarity searching; DNA METHYLTRANSFERASE INHIBITORS; TUMOR-SUPPRESSOR GENES; HUMAN CANCER; METHYLATION; DISCOVERY; DNMT1; REPAIR; CELLS; ASSAY; IDENTIFICATION; Chemistry, Medicinal; Pharmacology & Pharmacy
DNA hypomethylating drugs that act on DNA methyltransferase (DNMT) isoforms are promising anticancer agents. By using a well-characterized live-cell system to measure DNA methylation revisions (imprints), we characterize olsalazine, an approved anti-inflammatory drug, as a novel DNA hypomethylating agent. The cell-based screen used in this work is highly tractable, internally controlled, and well-suited for a drug repurposing strategy in epigenetics. Olsalazine very closely mimics the action of 5-aza-2-deoxycytidine, a known hypomethylating drug, with minimal cytotoxicity at the concentrations tested. Olsalazine was identified by a rapid computer-guided similarity search of a database of approved drugs to a previously identified inhibitor of DNMTs.
"Toward Drug Repurposing in Epigenetics: Olsalazine as a Hypomethylating Compound Active in a Cellular Context" (2014). Faculty Bibliography 2010s. 5829.