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

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127296. doi: 10.1016/j.bmcl.2020.127296. Epub 2020 Jun 1.


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 Kd 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.

Keywords: CBL0137; Curaxin; DNA methylation; Dnmt3a-CD; Doxorubicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / drug effects
  • DNA Methyltransferase 3A
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • CBLC137
  • Carbazoles
  • DNMT3A protein, human
  • Enzyme Inhibitors
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A