Decitabine: a historical review of the development of an epigenetic drug.
The development of decitabine from its synthesis in 1964 to the submission of a registration file has been described. Although the unique DNA-demethylating capacity of decitabine is known for a long time, its application is under continuing investigation. The use of decitabine in MDS, AML, CML, stem cell transplant, sickle cell anemia and thalassemia looks promising. The epigenetic dose seems lower than the cytotoxic dose. Whereas most drugs have matured after 40 years, decitabine is only at the beginning of a new development phase in epigenesis.
de Vos
Dick
D
Pharmachemie BV, Haarlem, The Netherlands. dick.d.vos@pharmachemie.com
van Overveld
Wendy
W
D000755:Anemia, Sickle Cell / Q000188:drug therapy; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D015195:Drug Design; D044127:Epigenesis, Genetic / Q000187:drug effects*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D019172:Transplantation Conditioning / Q000379:methods
D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine