Toward Drug Repurposing in Epigenetics: Olsalazine as a Hypomethylating Compound Active in a Cellular Context

    Authors

    O. Mendez-Lucio; J. Tran; J. L. Medina-Franco; N. Meurice;M. Muller

    Comments

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    Abbreviated Journal Title

    ChemMedChem

    Keywords

    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

    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.

    Journal Title

    Chemmedchem

    Volume

    9

    Issue/Number

    3

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    560

    Last Page

    565

    WOS Identifier

    WOS:000331795500013

    ISSN

    1860-7179

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