Fig. 1
From: The timeline of epigenetic drug discovery: from reality to dreams
Mechanism of action of azacitidine and decitabine. 5-Azacytidine (compound 1), after metabolic conversion (compound 3) and incorporation into DNA (compound 4), behaves as a suicide substrate for DNA methyltransferases. The enzyme carries out the usual nucleophilic attack by the active site Cys residue and methylation by S-adenosyl-l-methionine (SAM) but cannot undergo product release, being trapped instead as the covalent adduct 5, Decitabine (compound 2), has an identical mechanism of action, except that its metabolism to compound 3 does not require a deoxygenation step