Ricerc@Sapienza

The alteration of the DNA methylation pattern is often related to the onset of diseases based on epigenetic dysregulation, primarily cancer. In this scenery the development of DNA methyltransferase inhibitors is one of the most attractive challenges for anticancer therapy. The present chapter proposes a comprehensive classification of the DNA methyltransferase inhibitors known in literature, on the basis of their natural or synthetic nature and their mechanism of action.

DNA methyltransferases (DNMTs) play a relevant role in epigenetic control of cancer cell survival and proliferation. Since only two DNMT inhibitors (azacitidine and decitabine) have been approved to date for the treatment of hematological malignancies, the development of novel potent and specific inhibitors is urgent. Here we describe the design, synthesis, and biological evaluation of a new series of compounds acting at the same time as DNMTs (mainly DNMT3A) inhibitors and degraders.