5-Aza-2'-deoxycytidine

Breast Feeding; Lactation; Milk, Human; Antimetabolites; Antineoplastic Agents; Enzyme Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

5-aza-2'-deoxycytidine is a fine white crystalline powder. Used as a drug.

Solid

Danger

H302 (91.5%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 47 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

5-AZA-2'-DEOXYCYTIDINE is an organic compound with both amine and alcohol substituents. 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.

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 (NTP, 1992).

L01BC08

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Decitabine is a prodrug analogue of the natural nucleotide 2’-deoxycytidine, which, upon being phosphorylated intracellularly, is incorporated into DNA and exerts numerous effects on gene expression. The use of decitabine is associated with neutropenia and thrombocytopenia. In addition, decitabine can cause fetal harm in pregnant women; effective contraception and avoidance of pregnancy are recommended during treatment with decitabine.

Myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms that manifest in peripheral cytopenias and may eventually progress to secondary acute myeloid leukemia (sAML). Included in the over 45 genes commonly mutated in MDS patients are those involved in DNA methylation and histone modification, and it is well-established that alteration of the epigenetic landscape is a feature of myeloid leukemias. Decitabine is considered a prodrug, as it requires transport into cells and subsequent phosphorylation by distinct kinases to generate the active molecule 5-aza-2'-deoxycytidine-triphosphate, which is incorporated by DNA polymerase during DNA replication. Once incorporated into DNA, decitabine is recognized as a substrate by DNA methyltransferase enzymes (DNMTs), specifically DNMT1, but due to the presence of an N5 rather than C5 atom, traps the DNMT through the irreversible formation of a covalent bond. At low concentrations, this mode of action depletes DNMTs and results in global DNA hypomethylation while at high concentrations, it additionally results in double-strand breaks and cell death. The general hypothesis regarding decitabine's therapeutic efficacy is that the global hypomethylation it induces results in the expression of previously silent tumour suppressor genes. However, there are other putative mechanisms also related to this change in DNA methylation, including indirect alteration of transcription through effects on transcription factors, indirectly altering histone modifications and chromatin structure, and activating pathways involved in DNA damage response. The overall effect of decitabine is a decrease in neoplastic cell proliferation and an increase in the expression of tumour suppressor genes.