Toward drug repurposing in epigenetics: olsalazine as a hypomethylating compound active in a cellular context.
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.
Facultad 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).
Oscar
O
Méndez-Lucio
Jeremy
J
Tran
José L
JL
Medina-Franco
Nathalie
N
Meurice
Mark
M
Muller
D000636:Aminosalicylic Acids / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D058492:Drug Repositioning; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004247:DNA; C032587:olsalazine
DNA methylation; cancer; drug discovery; drug repurposing; hypomethylating agents; similarity searching