DNA methylation (and demethylation) is one of several regulators of gene transcription. Aberrant DNA methylation is an epigenetic mechanism that can inactivate the expression of certain genes involved in the suppression of tumorigenesis such as tumor suppressor genes, genes that suppress apoptosis, metastasis and angiogenesis, genes that repair DNA and genes that express tumor-associated antigens.
Four novel DNA methyl transferase inhibitors (DNMTIs) have been designed, synthesized and are being tested. Our lead nucleoside is different from the approved DNMTIs, such that it inhibits DNMT in both solid tumor and hematologic tumor cell lines and has shown activity in cell lines resistant to 5-azadC. It is more active as a DNMTI and less cytotoxic than 5-azaC.