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2353-33-5 molecular structure
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4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one

ChemBase ID: 1130
Molecular Formular: C8H12N4O4
Molecular Mass: 228.20528
Monoisotopic Mass: 228.08585488
SMILES and InChIs

SMILES:
O1[C@@H]([C@@H](O)C[C@@H]1n1c(=O)nc(nc1)N)CO
Canonical SMILES:
OC[C@H]1O[C@H](C[C@@H]1O)n1cnc(nc1=O)N
InChI:
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
InChIKey:
XAUDJQYHKZQPEU-KVQBGUIXSA-N

Cite this record

CBID:1130 http://www.chembase.cn/molecule-1130.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one
IUPAC Traditional name
decitabine
Brand Name
Dacogen
Synonyms
Azadc
DAC
Dezocitidine
5-aza-2'-deoxycytidine
decitabine
Decitabine
2′-Deoxy-5-azacytidine
4-Amino-1-(2-deoxy-β-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one
5-Aza-2′-deoxycytidine
Dacogen
CAS Number
2353-33-5
EC Number
219-089-4
MDL Number
MFCD00043011
Beilstein Number
617982
PubChem SID
160964593
46505657
24890797
PubChem CID
451668

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 13.894836  H Acceptors
H Donor LogD (pH = 5.5) -2.1646957 
LogD (pH = 7.4) -2.164695  Log P -2.1646948 
Molar Refractivity 50.6825 cm3 Polarizability 19.995268 Å3
Polar Surface Area 120.74 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P -1.96  LOG S -1.62 
Solubility (Water) 5.50e+00 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
acetic acid: water (1:1): soluble50 mg/mL expand Show data source
DMSO expand Show data source
Sparingly soluble expand Show data source
Melting Point
~200 °C (dec.) expand Show data source
Storage Condition
-20°C expand Show data source
RTECS
XZ3012000 expand Show data source
European Hazard Symbols
Toxic Toxic (T) expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Risk Statements
61-22-36/37/38-68 expand Show data source
Safety Statements
26-36/37 expand Show data source
GHS Pictograms
GHS07 expand Show data source
GHS08 expand Show data source
GHS Signal Word
Danger expand Show data source
GHS Hazard statements
H302-H315-H319-H335-H341-H360 expand Show data source
GHS Precautionary statements
P201-P261-P281-P305 + P351 + P338-P308 + P313 expand Show data source
Personal Protective Equipment
dust mask type N95 (US), Eyeshields, Gloves expand Show data source
Storage Temperature
-20°C expand Show data source
Target
Antimetabolites expand Show data source
Purity
≥97% expand Show data source
≥97.0% (HPLC) expand Show data source
Salt Data
Free Base expand Show data source
Shipped in
wet ice expand Show data source
Empirical Formula (Hill Notation)
C8H12N4O4 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
DrugBank - DB01262 external link
Item Information
Drug Groups approved; investigational
Description Decitabine 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.
Indication For treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups (scores ≥0.5).
Pharmacology Decitabine is an analogue of the natural nucleoside 2’-deoxycytidine. It functions in the same way as 5-Azacytidine. The antineoplastic activity of this drug is dependent on its intracellular conversion to its 5'-triphosphate metabolite.
Toxicity There is no known antidote for overdosage with decitabine. Higher doses are associated with increased myelosuppression including prolonged neutropenia and thrombocytopenia.
Affected Organisms
Humans and other mammals
Biotransformation The exact route of elimination and metabolic fate of decitabine is not known in humans. One of the pathways of elimination of decitabine appears to be deamination by cytidine deaminase found principally in the liver but also in granulocytes, intestinal epithelium and whole blood.
Half Life The terminal phase elimination half-life is 0.51 ± 0.31 hours.
Protein Binding Plasma protein binding of decitabine is negligible (<1%).
Clearance * 125 L/h/m2 [Patients receiving 15 mg/m2 3-hr infusion every 8 hours for 3 days]
* 210 L/h/m2 [20 mg/m2 1-hr infusion daily for 5 days]
References
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. [Pubmed]
Wijermans PW, Ruter B, Baer MR, Slack JL, Hussain SI, Lubbert M: Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res. 2007 Sep 17;. [Pubmed]
Daskalakis M, Blagitko-Dorfs N, Hackanson B: Decitabine. Recent Results Cancer Res. 2010;184:131-57. [Pubmed]
Saba HI, Wijermans PW: Decitabine in myelodysplastic syndromes. Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31. [Pubmed]
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. [Pubmed]
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. [Pubmed]
Oki Y, Aoki E, Issa JP: Decitabine--bedside to bench. Crit Rev Oncol Hematol. 2007 Feb;61(2):140-52. Epub 2006 Oct 4. [Pubmed]
External Links
Wikipedia
Drugs.com
Selleck Chemicals - S1200 external link
Research Area
Description Ovarian cancer,Myelodysplastic syndromes
Biological Activity
Description Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively.
Targets DNA methyltransferase (HL-60) DNA methyltransferase (KG1a)
IC50 100 ng/mL 1 ng/mL [1]
In Vitro Decitabine inhibits cell growth in a dose and time-dependent manner with IC50 of approximately 438 nM and 43.8 nM for 72 hours and 96 hours exposure in HL-60 and KG1a leukemic cells, respectively. [1] A recent study shows that Decitabine exhibits high anti-proliferative and pro-apoptotic activity against anaplastic large cell lymphoma (ALCL), and inhibits [3H]–thymidine uptake in KARPAS-299 cells with EC50 of 0.49 μM. [2]
In Vivo In a ALK+ KARPAS-299 murine xenograft model, Decitabine at a dose of 2.5 mg/kg causes increased apoptosis and reduced proliferation of tumor cells, and also results in demethylation of tumor suppressor p16INK4A. [2]
Clinical Trials Decitabine is currently in Phase I clinical trials in patients with Higher-risk MDS and MDS/AML Receiving Allogeneic Stem Cell Transplantation.
Features
Combination Therapy
Description Combination of Decitabine (100 ng/mL) and Trichostatin A (TSA) (3 ng/mL), a potent inhibitor of histone deacetylase, shows an additive effect on the DNA synthesis inhibition in both HL-60 and KG1a leukemic cell lines. Combination of Decitabine and TSA leads to greater growth inhibition of HL-60 and KG1a leukemic cells than either agent alone. [1] Combination treatment of Decitabine and Dasatinib is currently in Phase I clinical trials in patients with Accelerated or Blastic Phase Chronic Myelogenous Leukemia.
Protocol
Kinase Assay [1]
DNA synthesis assay The rate of DNA synthesis is measured by the incorporation of radioactive thymidine into DNA. HL-60 and KG1a cells are suspended in 2 mL RPMI medium containing 10% fetal serum in 6-well (35 mm diameter) dishes and incubated with different concentrations of corresponding drugs for 48 hours (drugs are added simultaneously). At 48 hours, 0.5 μCi [3H] thymidine (6.7 Ci/mmol) is added to each well and incubated for an additional 24 hours. The cells are placed on GF/C glass fiber filters (2.4 cm diameter), washed with cold 0.9% NaCl, 5% cold trichloroacetic acid and ethanol. The filters containing the DNA are then dried, placed in EcoLite scintillation liquid (ICN) and the radioactivity measured using Beckman LS 6000IC scintillation counter. The IC50 is defined as the concentration of drug that inhibits 50% of the DNA synthesis of the leukemic cell lines from the dose–response curve.
Cell Assay [1]
Cell Lines HL-60 and KG1a
Concentrations 0-500 nM
Incubation Time 96 hours
Methods For the growth inhibition assay, cells in log phase are placed in 5 mL of medium. Different concentrations of Decitabine are added to the medium simultaneously. Cell counts are performed at the indicated times using a model ZM Coulter Counter. The concentration that produces 50% inhibition of growth (IC50) is determined from the growth curves of the drug treated leukemic cell lines.
Animal Study [2]
Animal Models KARPAS-299 human cells are inoculated subcutaneously into the right and left flanks of the mice.
Formulation Decitabine is dissolved in sterile PBS .
Doses ≤2.5 mg/kg
Administration Administered via i.p.
References
[1] Shaker S, et al. Leuk Res, 2003, 27(5), 437-444.
[2] Hassler MR, et al. Biochimie, 2012, doi.org/10.1016/j.biochi.2012.05.029.
Sigma Aldrich - A3656 external link
Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
General description
Decitabine is an epigenetic modifier that inhibits DNA methyltransferase activity which results in DNA demethylation (hypomethylation) and gene activation by remodeling "opening" chromatin. Genes are synergistically reactivated when demethylation is combined with histone hyperacetylation.
Biochem/physiol Actions
5′-Azadeoxycytidine causes DNA demethylation or hemi-demethylation. DNA demethylation can regulate gene expression by "opening" the chromatin structure detectable as increased nuclease sensitivity. This remodeling of chromatin structure allows transcription factors to bind to the promoter regions, assembly of the transcription complex, and gene expression.
Sigma Aldrich - 11390 external link
Other Notes
A very potent cytotoxic agent to tumour cells in vitro at concentrations that do not inhibit macromolecular synthesis1

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • 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. Pubmed
  • • Wijermans PW, Ruter B, Baer MR, Slack JL, Hussain SI, Lubbert M: Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res. 2007 Sep 17;. Pubmed
  • • Saba HI, Wijermans PW: Decitabine in myelodysplastic syndromes. Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31. Pubmed
  • • 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. Pubmed
  • • 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. Pubmed
  • • Oki Y, Aoki E, Issa JP: Decitabine--bedside to bench. Crit Rev Oncol Hematol. 2007 Feb;61(2):140-52. Epub 2006 Oct 4. Pubmed
  • • Daskalakis M, Blagitko-Dorfs N, Hackanson B: Decitabine. Recent Results Cancer Res. 2010;184:131-57. Pubmed
  • • Shaker S, et al. Leuk Res, 2003, 27(5), 437-444.
  • • Hassler MR, et al. Biochimie, 2012, doi.org/10.1016/j.biochi.2012.05.029.
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PATENTS

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