Category: Modified nucleosides
Registration & producers: Vidaza 2004 (Pharmion, Celgene), Dacogen 2006 (MGI Pharma, Otsuka America Pharmaceutical, Inc.)
Studies on 6-azapyrimidines and 5-azapyrimidines and their nucleosides conducted at IOCB resulted in the discovery of potent antimetabolites. The cytidine analogues 5-azacytidine and 2-deoxy-5-azacytidine were first synthesized, patented, and published by Alois Pískala in the mid-1960s. It would take 40 years to introduce these cytostatics to the market (Vidaza by Pharmion Corporation in 2004 and Dacogen by MGI Pharma in 2006), long after the original patents had expired.
Since patent protection was no longer available, they received orphan drug designation for the treatment of myelodysplastic syndromes and later for the treatment of acute myeloid leukemia. Both are members of a new class of drugs working on the epigenetic principle as DNA demethylating agents. They cause hypomethylation of some tumor suppressor genes by inhibiting DNA methyltransferase.