5-aza-2′-deoxycytidine
 |
|
| Clinical data | |
|---|---|
| Trade names | Dacogen |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608009 |
| License data | |
| Pregnancy category |
|
| Routes of administration |
Intravenous |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Protein binding | <1% |
| Biological half-life | 30 minutes |
| Identifiers | |
|
|
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| ECHA InfoCard | 100.017.355 |
| Chemical and physical data | |
| Formula | C8H12N4O4 |
| Molar mass | 228.206 g/mol |
| 3D model (JSmol) | |
|
|
|
|
  (what is this?)
|
|
Decitabine (trade name Dacogen), or 5-aza-2'-deoxycytidine, acts as an Nucleic Acid Synthesis Inhibitor. It is a drug for the treatment of myelodysplastic syndromes, a class of conditions where certain blood cells are dysfunctional, and for acute myeloid leukemia (AML). Chemically, it is a cytidine analog.
Decitabine is used to treat myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System groups. In patients with renal insufficiency, Batty and colleagues reported the first case series on the feasibility of therapy with hypomethylating agents in patients with renal insufficiency.
It also has EU approval for acute myeloid leukemia (AML).
Decitabine is a hypomethylating agent. It hypomethylates DNA by inhibiting DNA methyltransferase.
It functions in a similar manner to azacitidine, although decitabine can only be incorporated into DNA strands while azacitidine can be incorporated into both DNA and RNA chains.
It incorporates into DNA strands upon replication, and then when DNA methyltransferases (DNMTs) such as DNMT1, are engaged to bind the DNA and to replicate the methylation to the daughter strand, DNMTs are bound to decitabine irreversibly and cannot disengage. Therefore, the action of decitabine is division-dependant, meaning the cells have to divide in order for the pharmaceutical to act. Therefore, cancer cells which divide much more rapidly than most other cells in the body will be more severely affected by decitabine just because they replicate more. In cancer cells, and more specifically in haematological malignancies, it seems that DNA hypermethylation is really critical for their development. Methylation of CpG islands upstream of tumor suppressor genes in order to silence them seems to be critical for these type of cancers. So decitabine, at optimal, lower-than-in-the-past doses is blocking this type of methylation and it has an anti-neoplastic effect.
...
Wikipedia