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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:32:42 UTC
HMDB IDHMDB15391
Secondary Accession NumbersNone
Metabolite Identification
Common NameDecitabine
DescriptionDecitabine is indicated for treatment of patients with myelodysplastic syndrome (MDS). It is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Cells in the presence of Decitabine incorporate it into DNA during replication and RNA during transcription. The incorporation of Decitabine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence. This adversely affects the way that cell regulatory proteins are able to bind to the DNA/RNA substrate.
Structure
Thumb
Synonyms
ValueSource
4-amino-1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-S-triazin-2(1H)-oneChEBI
5-AzadeoxycytidineChEBI
4-amino-1-(2-Deoxy-b-D-erythro-pentofuranosyl)-S-triazin-2(1H)-oneGenerator
4-amino-1-(2-Deoxy-β-D-erythro-pentofuranosyl)-S-triazin-2(1H)-oneGenerator
5-Aza-2'-deoxycytidineHMDB
AzadcHMDB
DezocitidineHMDB
Chemical FormulaC8H12N4O4
Average Molecular Weight228.2053
Monoisotopic Molecular Weight228.085854892
IUPAC Name4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one
Traditional Namedecitabine
CAS Registry Number2353-33-5
SMILES
NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
InChI Identifier
InChI=1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1
InChI KeyInChIKey=XAUDJQYHKZQPEU-KVQBGUIXSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1,3,5-triazine ribonucleosides and ribnucleotides. These are nucleosides or nucleotides with a structure that consists of a a 1,3,5-triazine ring, which is N-linked to a ribose (or deoxyribose). Nucleotides have a phosphate group linked to the C5 carbon of the ribose (or deoxyribose) moiety.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
Class1,3,5-triazine ribonucleosides and ribnucleotides
Sub ClassNot Available
Direct Parent1,3,5-triazine ribonucleosides and ribnucleotides
Alternative Parents
Substituents
  • 1,3,5-triazine ribonucleoside or ribnucleotide
  • Triazinone
  • Amino-1,3,5-triazine
  • 1,3,5-triazine
  • Triazine
  • Primary aromatic amine
  • Saccharide
  • Heteroaromatic compound
  • Oxolane
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Teratogens
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.50e+00 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility5.5 mg/mLALOGPS
logP-2ALOGPS
logP-2.2ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)13.89ChemAxon
pKa (Strongest Basic)-0.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area120.74 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity50.68 m3·mol-1ChemAxon
Polarizability21.15 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01262
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01262
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01262
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID397844
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDecitabine
NuGOwiki LinkHMDB15391
Metagene LinkHMDB15391
METLIN IDNot Available
PubChem Compound451668
PDB IDNot Available
ChEBI ID50131
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Daskalakis M, Blagitko-Dorfs N, Hackanson B: Decitabine. Recent Results Cancer Res. 2010;184:131-57. [20072836 ]
  2. Saba HI, Wijermans PW: Decitabine in myelodysplastic syndromes. Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31. [16015501 ]
  3. Jabbour E, Issa JP, Garcia-Manero G, Kantarjian H: Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies. Cancer. 2008 Jun;112(11):2341-51. [18398832 ]
  4. Stresemann C, Lyko F: Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer. 2008 Jul 1;123(1):8-13. [18425818 ]
  5. Oki Y, Aoki E, Issa JP: Decitabine--bedside to bench. Crit Rev Oncol Hematol. 2007 Feb;61(2):140-52. Epub 2006 Oct 4. [17023173 ]
  6. Wijermans PW, Ruter B, Baer MR, Slack JL, Saba HI, Lubbert M: Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res. 2008 Apr;32(4):587-91. Epub 2007 Sep 18. [17881052 ]
  7. Appleton K, Mackay HJ, Judson I, Plumb JA, McCormick C, Strathdee G, Lee C, Barrett S, Reade S, Jadayel D, Tang A, Bellenger K, Mackay L, Setanoians A, Schatzlein A, Twelves C, Kaye SB, Brown R: Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J Clin Oncol. 2007 Oct 10;25(29):4603-9. [17925555 ]

Enzymes

General function:
Involved in ATP binding
Specific function:
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
Molecular weight:
30518.315
References
  1. Schwarzenberg J, Radu CG, Benz M, Fueger B, Tran AQ, Phelps ME, Witte ON, Satyamurthy N, Czernin J, Schiepers C: Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway. Eur J Nucl Med Mol Imaging. 2011 Apr;38(4):711-21. Epub 2010 Dec 3. [21127859 ]
General function:
Involved in DNA binding
Specific function:
Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9.
Gene Name:
DNMT1
Uniprot ID:
P26358
Molecular weight:
184817.425
References
  1. Ando T, Nishimura M, Oka Y: Decitabine (5-Aza-2'-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells. Leukemia. 2000 Nov;14(11):1915-20. [11069027 ]
  2. Karpf AR, Moore BC, Ririe TO, Jones DA: Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine. Mol Pharmacol. 2001 Apr;59(4):751-7. [11259619 ]
  3. Csankovszki G, Nagy A, Jaenisch R: Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol. 2001 May 14;153(4):773-84. [11352938 ]
  4. Takebayashi S, Nakao M, Fujita N, Sado T, Tanaka M, Taguchi H, Okumura K: 5-Aza-2'-deoxycytidine induces histone hyperacetylation of mouse centromeric heterochromatin by a mechanism independent of DNA demethylation. Biochem Biophys Res Commun. 2001 Nov 9;288(4):921-6. [11688997 ]
  5. Saunthararajah Y, Hillery CA, Lavelle D, Molokie R, Dorn L, Bressler L, Gavazova S, Chen YH, Hoffman R, DeSimone J: Effects of 5-aza-2'-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003 Dec 1;102(12):3865-70. Epub 2003 Aug 7. [12907443 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Daskalakis M, Blagitko-Dorfs N, Hackanson B: Decitabine. Recent Results Cancer Res. 2010;184:131-57. [20072836 ]
  8. Saba HI, Wijermans PW: Decitabine in myelodysplastic syndromes. Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31. [16015501 ]
  9. Jabbour E, Issa JP, Garcia-Manero G, Kantarjian H: Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies. Cancer. 2008 Jun;112(11):2341-51. [18398832 ]
  10. Stresemann C, Lyko F: Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer. 2008 Jul 1;123(1):8-13. [18425818 ]
  11. Oki Y, Aoki E, Issa JP: Decitabine--bedside to bench. Crit Rev Oncol Hematol. 2007 Feb;61(2):140-52. Epub 2006 Oct 4. [17023173 ]