ContaminantDB: Azacitidine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (3)XML

Record Information

Version

1.0

Creation Date

2014-09-11 02:04:27 UTC

Update Date

2026-03-31 17:00:20 UTC

Accession Number

CHEM003634

Identification

Common Name

Azacitidine

Class

Small Molecule

Description

Azacitidine is only found in individuals that have used or taken this drug. It is a pyrimidine nucleoside analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein. Its incorporation into DNA leads to a covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequent cytotoxicity.

Contaminant Sources

HMDB Contaminants - Urine
IARC Carcinogens Group 2A
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amine
Antimetabolite, Antineoplastic
Drug
Enzyme Inhibitor
Ether
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
4-Amino-1-beta-D-ribofuranosyl-S-triazin-2(1H)-one	ChEBI
Azacitidina	ChEBI
Azacitidinum	ChEBI
Vidaza	Kegg
4-Amino-1-b-D-ribofuranosyl-S-triazin-2(1H)-one	Generator
4-Amino-1-β-D-ribofuranosyl-S-triazin-2(1H)-one	Generator
5 AZC	HMDB
Azacytidine	HMDB
Pharmion brand OF azacitidine	HMDB
5 Azacytidine	HMDB
Azacitidine	ChEBI

Chemical Formula

C₈H₁₂N₄O₅

Average Molecular Mass

244.205 g/mol

Monoisotopic Mass

244.081 g/mol

CAS Registry Number

320-67-2

IUPAC Name

4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one

Traditional Name

azacitidine

SMILES

NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

InChI Identifier

InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1

InChI Key

NMUSYJAQQFHJEW-KVTDHHQDSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as glycosylamines. Glycosylamines are compounds consisting of an amine with a beta-N-glycosidic bond to a carbohydrate, thus forming a cyclic hemiaminal ether bond (alpha-amino ether).

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbohydrates and carbohydrate conjugates

Direct Parent

Glycosylamines

Alternative Parents

Substituents

N-glycosyl compound
Pentose monosaccharide
Amino-1,3,5-triazine
Aminotriazine
Triazinone
Monosaccharide
Triazine
1,3,5-triazine
Heteroaromatic compound
Tetrahydrofuran
Secondary alcohol
Oxacycle
Azacycle
Organoheterocyclic compound
Amine
Primary amine
Primary alcohol
Alcohol
Organonitrogen compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organic nitrogen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

nucleoside analogue (CHEBI:2038 )
N-glycosyl-1,3,5-triazine (CHEBI:2038 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	229°C
Boiling Point	Not Available
Solubility	8.9E+004 mg/L

Predicted Properties

Property	Value	Source
Water Solubility	12.1 g/L	ALOGPS
logP	-2.4	ALOGPS
logP	-3.1	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	12.55	ChemAxon
pKa (Strongest Basic)	-0.38	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	140.97 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	52.19 m³·mol⁻¹	ChemAxon
Polarizability	21.5 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-08nc-9420000000-deb4c3c2e01ce611d805	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-0072-9783700000-4e1593dee5d4eee4fa53	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0910000000-bf3b4f701f0a4e9f2cd8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-6900000000-5d329d9eaea6433ed7cb	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03dm-9300000000-9df054033868819ef47c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udl-4690000000-2cfa5eaefe0d852fc770	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ox-9600000000-c47176436749bbaa6201	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00l6-9100000000-71ffe7618fd437f42131	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0900000000-ad27e26e064f360f3006	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-4900000000-5d9421c40d3f45d9dc69	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03ka-9500000000-79a738f312e868981bd2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01ox-1960000000-94c1bdd861f9dd5e7a9e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9500000000-0f6f7a947b16f6e8119a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-9000000000-6ba499348317121c0ac2	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Azacitidine is rapidly absorbed after subcutaneous administration. The bioavailability of subcutaneous azacitidine relative to IV azacitidine is approximately 89%, based on area under the curve.

Mechanism of Toxicity

Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein. Its incorporation into DNA leads to a covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequent cytotoxicity.

Metabolism

An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine may be metabolized by the liver. The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known. Route of Elimination: Following IV administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over three days. Mean excretion of radioactivity in urine following SC administration of 14C-azacitidine was 50%. Half Life: Mean elimination half-life is approximately 4 hours.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2A, probably carcinogenic to humans. (14)

Uses/Sources

For treatment of patients with the following French-American-British myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation (now classified as acute myelogenous leukemia with multilineage dysplasia), and chronic myelomonocytic leukemia.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB00928

HMDB ID

HMDB0015063

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Lorenzo DE FERRA, Maurizio ZENONI, Stefano TURCHETTA, Mauro ANIBALDI, Ettore AMMIRATI, Paolo BRANDI, Giorgio BERARDI, “PROCESS FOR THE SYNTHESIS OF AZACITIDINE AND DECITABINE.” U.S. Patent US20110245485, issued October 06, 2011.