Decitabine

Catalog No.S1200

Decitabine is a potent inhibitor of DNA methylation, used to treat myelodysplastic syndrome (MDS).

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Decitabine Chemical Structure

Decitabine Chemical Structure
Molecular Weight: 228.21

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Product Information

  • Compare DNA Methyltransferase Inhibitors
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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Decitabine is a potent inhibitor of DNA methylation, used to treat myelodysplastic syndrome (MDS).
Targets DNA methylation [1]
(HL-60, KG1a cells)
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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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... Click to View More Cell Line Experimental Data

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]
Features

Protocol(Only for Reference)

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
Method 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 .
Dosages ≤2.5 mg/kg
Administration Administered via i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

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.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02795923 Not yet recruiting Lung Cancer|Non-small Cell Lung Cancer Yogen Saunthararajah|Case Comprehensive Cancer Center September 2016 Phase 2
NCT02847000 Not yet recruiting Metastatic Pancreatic Adenocarcinoma Yogen Saunthararajah|Case Comprehensive Cancer Center September 2016 Phase 0
NCT02846935 Not yet recruiting T-cell Lymphoma|Aggressive B-cell Lymphoma|Non-Hodgkins Lymphomas|Indolent B-cell Lymphoma Yogen Saunthararajah|Case Comprehensive Cancer Center September 2016 Phase 0
NCT02664181 Not yet recruiting Advanced Non-Small Cell Lung Cancer Yogan Saunthararajah|Case Comprehensive Cancer Center July 2016 Phase 2
NCT02839694 Recruiting Neoplasm Metastasis|Sarcoma|Neoplasms, Germ Cell and Embryonal|Melanoma National Cancer Institute (NCI)|National Institutes of He  ...more National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) July 2016 Phase 1

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Chemical Information

Download Decitabine SDF
Molecular Weight (MW) 228.21
Formula

C8H12N4O4

CAS No. 2353-33-5
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms Deoxycytidine
Solubility (25°C) * In vitro DMSO 45 mg/mL (197.18 mM)
Water 10 mg/mL (43.81 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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