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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Toward drug repurposing in epigenetics: olsalazine as a hypomethylating compound active in a cellular context
Oscar Méndez-Lucio1, Jeremy Tran, José L Medina-Franco
1Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510 (Mexico); Current address: Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (UK).
Abstract:
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.
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