General Description
Fine white crystalline powder. Used as a drug.
Reactivity Profile
5-AZA-2'-DEOXYCYTIDINE(2353-33-5) is an aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Air & Water Reactions
Probably light and air sensitive. Water soluble. Decomposes in aqueous solution at a rate that depends on pH: at pH 7 the drug is more stable than at pH 9, but is less stable than at pH 6. At pH 7 and 99°F, approximately 7% conversion occurs in 1 hour .
Fire Hazard
Flash point data for this chemical are not available. 5-AZA-2'-DEOXYCYTIDINE is probably combustible.
Description
Decitabine, 5-aza-2’-deoxycytidine, has been launched for the treatment of
myelodysplastic syndromes (MDS). MDS are a set of hematologic disorders
affecting the bone marrow that result in ineffective formation and development
of blood cells. Furthermore, patients with MDS have a high risk of progressing to
acute myeloid leukemia (AML). Traditional treatments include blood transfusions,
hematopoietic growth factors, and prophylactic antibiotics, but these
measures merely improve the quality of life with questionable effects on disease
modification. While stem-cell transplantation is an aggressive, potentially curative
approach, the advanced age or the other complicating health issues of most
patients preclude them from considering this option. Recent advances in the
underlying etiology of MDS, however, have led to the development of a new
class of compounds known as ‘‘demethylating agents’’. Decitabine follows the
successful introduction of the first DNA methyltransferase inhibitor azacitidine.
Chemical Properties
white crystalline powder
Originator
Pharmachemie (Netherlands)
Uses
Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively
Uses
Used as cancer treatment, in particular to inhibit the growth of pancreatic endocrine tumor cell lines.
Definition
ChEBI: 5-aza-2'-deoxycytidine is a 2'-deoxyribonucleoside.
Brand name
Dacogen (Millot Laboratories, France).
Biological Activity
Cytosine analog that once incorporated into DNA acts as a suicide substrate for DNA methyltransferase. Inhibits DNA methyltransferase and results in DNA hypomethylation and activation of silent genes. Chemotherapeutic agent; suppresses growth of human tumor cell lines. Demethylates differentiation-related genes; reverses embryonic stem cell differentiation.
Biochem/physiol Actions
Primary TargetDNA methyltransferase inhibitor
Clinical Use
Antineoplastic antimetabolite agent:
Treatment of acute myeloid leukaemia
Safety Profile
Poison by intravenous route.Human mutation data reported. When heated todecomposition it emits toxic fumes of NOx.
Synthesis
Silylated 5-aza-cytosine (28) was condensed with 9-
fluorenylmethoxycarbonyl (Fmoc) protected 2-deoxy-1-chlororibose
(27) with tin chloride (IV) in dichloroethane (Scheme
4). The coupled product 29 was de-protected with excess
triethylamine in dry pyridine to give decitabine (IV) in 36%
yield after separation from its corresponding |áisomer.
target
Telomerase | DNA Methyltransferase | p21
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine, increased risk
of agranulocytosis.
Metabolism
The exact route of metabolism and elimination is
unknown but thought to be through deamination
by cytidine deaminase in the liver, kidney, intestinal
epithelium and blood to form inactive metabolites.
References
1) Bender et al. (1998), Inhibition of DNA methylation by 5-aza-2′-deoxycytidine suppresses the growth of human tumor cell lines; Cancer Res., 58 95
2) El-Serafi et al. (2011), Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A; Differentiation, 81 35
