Azacitidine 320-67-2

Uses

Azacitidine is mainly used in the treatment of myelodysplastic syndrome (MDS), for which it received approval by the U. S. Food and Drug Administration on May 19, 2004; it is marketed as Vidaza. In a randomized controlled trial comparing azacitidine to supportive treatment of MDS, around 16% of people receiving the drug had a complete or partial response—blood cell counts and bone marrow morphology returning to normal—and 2/3 patients who required blood transfusions before the study no longer needed them after receiving azacitidine. It can also be used in vitro to remove methyl groups from DNA. This may weaken the effects of gene silencing mechanisms that occurred prior to the methylation. Methylation events are therefore believed to secure the DNA in a silenced state. Demethylation may reduce the stability of silencing signals and thus confer relative gene activation.

Mechanism of action

Cells in the presence of azacitidine incorporate it into DNA during replication and RNA during transcription. The incorporation of azacitidine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence, affecting the way that cell regulation proteins are able to bind to the DNA/RNA substrate. Inhibition of DNA methylation occurs through the formation of stable complexes between the molecule and with DNA methyltransferases, thereby saturating cell methylation machinery.