DNA methyltransferase inhibitors in cancer: a chemical and therapeutic patent overview and selected clinical studies

Expert Opin Ther Pat. 2012 Dec;22(12):1427-42. doi: 10.1517/13543776.2012.729579. Epub 2012 Oct 3.


Introduction: DNA methylation is an epigenetic modification that modulates gene expression without altering the DNA base sequence. It plays a crucial role in cancer by silencing tumor suppressor genes (TSG). The DNA methyltransferases (DNMT) are the enzymes that catalyze DNA methylation and they are interesting therapeutical targets since DNA methylation is reversible such that an aberrant hypermethylation of DNA can be reverted by inhibition of DNMTs. Today, two drugs are on the market for the treatment of myelodysplastic syndrome, azacitidine and decitabine.

Areas covered: Here, we present a review of the patents describing the chemistry and biological activities of novel DNMT inhibitors and discuss select clinical studies.

Expert opinion: DNMT inhibitors have shown efficacy in clinics. However, highly efficient and specific DNMT inhibitors have not yet been identified. Improving methods will certainly lead to the prediction of novel directly binding inhibitors in the future.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line
  • DNA Methylation / drug effects
  • DNA Modification Methylases / antagonists & inhibitors*
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • High-Throughput Screening Assays
  • Humans
  • Molecular Structure
  • Patents as Topic*
  • Protein Conformation
  • Structure-Activity Relationship
  • Transfection


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • DNA Modification Methylases