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ID: ALA4622935

Journal: Bioorg Med Chem Lett

Title: Novel anticancer drug curaxin CBL0137 impairs DNA methylation by eukaryotic DNA methyltransferase Dnmt3a.

Authors: Sergeev A, Vorobyov A, Yakubovskaya M, Kirsanova O, Gromova E.

Abstract: Novel DNA intercalating anticancer drug curaxin CBL0137 significantly inhibited in vitro DNA methylation by eukaryotic DNA methyltransferase Dnmt3a catalytic domain (Dnmt3a-CD) at low micromolar concentrations (IC₅₀ 3-9 µM). CBL0137 reduced the binding affinity of Dnmt3a-CD to its DNA target, causing up to four-fold increase in the K_d of the enzyme/DNA complex. Binding of CBL0137 to Dnmt3a-CD was not observed. The observed decrease in methylation activity of Dnmt3a-CD in the presence of CBL0137 can be explained by curaxin's ability to intercalate into DNA.

CiteXplore: 32631516

DOI: 10.1016/j.bmcl.2020.127296