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Toward Drug Repurposing in Epigenetics: Olsalazine as a Hypomethylating Compound Active in a Cellular Context
Author(s) -
MéndezLucio Oscar,
Tran Jeremy,
MedinaFranco José L.,
Meurice Nathalie,
Muller Mark
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300555
Subject(s) - hypomethylating agent , drug repositioning , epigenetics , context (archaeology) , drug , dna methylation , methyltransferase , pharmacology , dna , computational biology , biology , methylation , biochemistry , gene , paleontology , gene expression
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.