Title

Toward Drug Repurposing In Epigenetics: Olsalazine As A Hypomethylating Compound Active In A Cellular Context

Keywords

cancer; DNA methylation; drug discovery; drug repurposing; hypomethylating agents; similarity searching

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. A bold new direction: Using a novel DNA methylation reprogramming system that operates in the context of living cells, we report the characterization of olsalazine, an anti-inflammatory drug, as a new DNA hypomethylating agent. The results come from cell-based assays that monitor the activity of DNA methyltransferase (DNMT) in living cells. © 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Publication Date

3-1-2014

Publication Title

ChemMedChem

Volume

9

Issue

3

Number of Pages

560-565

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/cmdc.201300555

Socpus ID

84896691228 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84896691228

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