Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
GHS classification
GHS Classification · 4 items
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.
Hazard information
Fire HazardsFlash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
Reactive GroupAlcohols and Polyols
Reactivity Profile · 1 item
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.
Air and Water Reactions · 1 item
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).
Hazard Classes and CategoriesAcute Tox. 4 (91.5%)
Chemistry & industry
Pharmacology
ATC Code · 3 items
L01BC08
L - Antineoplastic and immunomodulating agents
QL - Antineoplastic and immunomodulating agents
Protein BindingDecitabine exhibits negligible (< 1%) plasma protein binding.
Pharmacodynamics · 1 item
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.
Mechanism of Action · 1 item
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.
50 in · LD50 in mice (mg/kg): 190 i.p. (Momparler, 1985)
Safety & protection
Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
First Aid · 1 item
EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.
Nonfire Spill Response · 1 item
SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.
Personal Protective Equipment (PPE) · 1 item
RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)
Toxicology
Hepatotoxicity · 1 item
In early clinical trials using high doses of decitabine, serum enzyme elevations occurred in up to 16% of patients with underlying liver disease or liver metastases, but rarely in persons without hepatic illness. In subsequent studies, serum ALT elevations were reported in 5% to 15% of treated patients, but all were self-limited and no clinically apparent liver injury was reported. Recent studies have reported elevations in serum bilirubin levels in 7% to 12% of treated patients, but the elevations resolved rapidly and were not associated with other clinical or laboratory evidence of liver injury. Monitoring of serum enzyme levels during treatment is recommended only in patients with concurrent liver disease.
Drug Induced Liver Injury · 6 items
Drug Induced Liver Injury Rank (DILIrank 2.0)
Decitabine
Ambiguous-DILI-concern
4
Adverse reactions
DOI:10.1016/j.drudis.2016.02.015
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
Safety data
F
10-34
PPE
dust mask type N95 (US), Eyeshields, Gloves
wgk
3
rtecs
XZ3012000
hs_code
29349990
Toxicity
LD50 in mice (mg/kg): 190 i.p. (Momparler, 1985)
risk_code
22-36/37/38-68-61
Signal word
Danger
Symbol(GHS)
GHS07,GHS08
hazard_code
Xn,Xi,T
safety_code
26-36-36/37
Storage Class
6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Decitabine has a half-life of 0.62 hours (49% CV) when administered intravenously at 15 mg/m<sup>2</sup> for three hours every eight hours over three days, and a half-life of 0.54 hours (43% CV) at 20 mg/m<sup>2</sup> for one hour once daily over five days.
Metabolism/Metabolites · 1 item
Decitabine is phosphorylated inside cells by the sequential action of deoxycytidine kinase, nucleotide monophosphate kinase, and nucleotide diphosphate kinase, prior to being incorporated into newly synthesized DNA by DNA polymerase. Decitabine not incorporated into cellular DNA undergoes deamination by cytidine deaminase followed by additional degradation prior to excretion.
FDA Pharmacological Classification · 6 items
776B62CQ27
DECITABINE
Mechanisms of Action [MoA] - Nucleic Acid Synthesis Inhibitors
Established Pharmacologic Class [EPC] - Nucleoside Metabolic Inhibitor
Decitabine is a Nucleoside Metabolic Inhibitor. The mechanism of action of decitabine is as a Nucleic Acid Synthesis Inhibitor.
DECITABINE
MeSH Pharmacological Classification · 2 items
Antimetabolites that are useful in cancer chemotherapy.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Absorption, Distribution and Excretion · 4 items
Decitabine administered intravenously at 15 mg/m2 for three hours every eight hours over three days resulted in a Cmax of 73.8 ng/mL (66% coefficient of variation, CV), an AUC0-∞ of 163 ng\*h/mL (62% CV), and a cumulative AUC of 1332 ng\*h/mL (95% CI of 1010-1730). Similarly, decitabine at 20 mg/m2 for one hour once daily over five days resulted in a Cmax of 147 ng/mL (49% CV), an AUC0-∞ of 115 ng\*h/mL (43% CV), and a cumulative AUC of 570 ng\*h/mL (95% CI of 470-700).
Less than 1% of administered decitabine is excreted in the urine.
Decitabine as an apparent volume of distribution of 4.59 ± 1.42 L/kg.
Decitabine has a clearance of 125 L/hr/m<sup>2</sup> (53% CV) when administered intravenously at 15 mg/m<sup>2</sup> for three hours every eight hours over three days, and a clearance of 210 L/hr/m<sup>2</sup> (47% CV) at 20 mg/m<sup>2</sup> for one hour once daily over five days.
Cellular LocationsCytoplasm
Applications · 5 items
DescriptionDecitabine, 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.
UsesUsed as cancer treatment, in particular to inhibit the growth of pancreatic endocrine tumor cell lines.
UsesDecitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively
Uses5-Aza-2′-deoxycytidine has been used as a demethylating agent in breast cancer cell line, chromatin, DNA and promoter region of p16 gene.
General DescriptionFine white crystalline powder. Used as a drug.
