Demethylating agent


Demethylating agents are chemical substances that can inhibit methylation, resulting in the expression of the previously hypermethylated silenced genes. Cytidine analogs such as 5-azacytidine and 5-azadeoxycytidine are the most commonly used demethylating agents. They work by inhibiting DNA methyltransferases. Both compounds have been approved in the treatment of myelodysplastic syndrome by Food and Drug Administration in United States. Azacitidine and decitabine are marketed as Vidaza and Dacogen respectively. Azacitidine is the first drug to be approved by FDA for treating MDS and has been given orphan drug status. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells.

Mechanism of Action

There is very little known about the mechanism of action of these drugs. However, it was shown in 2015 that a possible mechanism of action of these drugs in colorectal cancer-initiating cells is through activating dsRNA expression which leads to the activation of the MDA5/MAVS RNA recognition pathway inducing some sort of viral mimicry inside the cell.