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[1] US20230172936A1
Purity: ≥98%
Decitabine (also known as Deoxycytidine; 5-aza-dCyd; NSC 127716; 5-Aza-2'-deoxycytidine; deoxyazacytidine; dezocitidine; Brand name: Dacogen. Abbreviations: 5AZA; DAC) is a potent and orally bioactive inhibitor of DNA methylation (DNA methyltransferase) that is commonly used to treat myelodysplastic syndrome (MDS) and cute myeloid leukemia (AML). Decitabine is a kind of deoxycytidine analog and an inducer of cellular differentiation. Decitabine has been shown substantial efficacy in reactivating epigenetically silenced tumor suppressor genes in vitro. In T24 bladder cancer cells, decitabine can increase histone H3-lysine 9 acetylation and histone H3-lysine 4 methylation at the unmethylated p14 promoter.
Targets |
DNMT1; DNMT3A; DNMT3B
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ln Vitro |
Decitabine therapy significantly decreased cell proliferation of SNU719, NCC24, and KATOIII after 96 h following exposure to Decitabine. Decitabine causes G2/M arrest and death in EBVaGC, decreases invasion ability, and upregulates E-cadherin expression in EBVaGC [1]. Only high dosages (10 μM) of Decitabine (0.1-1 μM; 24-72 hours) produce G2 arrest, accompanied by a reduction in G1 cells [3]. Decitabine upregulates DCTPP1 and dUTPase expression in HeLa cells [4].
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ln Vivo |
In female CD-1 mice, decitabine (1.0 mg/kg, po) in combination with tetrahydrouridine (THU) results in severe toxicity and increases susceptibility to decitabine toxicity related to decitabine plasma levels [5]. C57BL/6 mice with established EL4 tumors show regression when given decitabine (1.0 mg/kg; i.p.; once daily for 5 days) [7].
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Enzyme Assay |
Incorporation assay [8]
Twenty-four hours before treatment, cells were seeded in triplicate in 12-well plates, at a density of 2 × 105 cells per well and then incubated with 100 nM [3H]-decitabine (or other concentrations, if indicated). After incubation for 24 h (or other time periods, if indicated), cells were washed with phosphate buffered saline (PBS). For incorporation measurements, DNA or RNA was purified using DNeasy Blood and Tissue kit or RNeasy kit, respectively, and quantified by a ultraviolet (UV) photometer. The purified samples were mixed with liquid scintillation cocktail and their radioactivity was measured by liquid scintillation counting. Measurements were normalized to the amount of DNA (or RNA). The percentage of substitution of decitabine for cytosine was calculated as the amount of decitabine incorporated as a fraction of total cytosine, as described previously. For competition experiments, cells were either treated with 100 nM [3H]-decitabine in addition with increasing concentrations (100 nM, 500 nM, 1 μM, 2 μM) of [14C]-deoxycytidine or were treated with 100 nM [14C]-deoxycytidine in addition with increasing concentrations (100 nM, 500 nM, 1 μM, 2 μM) of [3H]-decitabine. After 24 h, cells were washed with PBS, DNA was extracted using DNeasy Blood and Tissue kit and was measured using liquid scintillation counting. DNA methylation analysis[8] Genomic DNA was isolated from cells using the DNeasy Blood and Tissue kit. Global DNA methylation levels were determined by capillary electrophoresis, as described previously. |
Cell Assay |
Cell Cycle Analysis[1]
Cell Types: HCT116 cells Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: Only high drug concentrations (10 µM) resulted in a G2 phase arrest, which was accompanied by a reduction of cells in G1 phase. |
Animal Protocol |
Animal/Disease Models: C57BL/6 mice (bearing EL4 cells)[6]
Doses: 1.0 mg/kg Route of Administration: intraperitoneal (ip)injection; one time/day for 5 days consecutive Experimental Results: Caused continuous tumor regression even after Decitabine treatment was stopped. |
References |
[1]. Nakamura M, et al. Decitabine inhibits tumor cell proliferation and up-regulates E-cadherin expression in Epstein-Barr virus-associated gastric cancer. J Med Virol. 2016 Jul 19.
[2]. Parker WB. Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem Rev. 2009 Jul;109(7):2880-93. [3]. Hagemann S, et al. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS One. 2011 Mar 7;6(3):e17388. [4]. Requena CE, et al. The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine. Biochem J. 2016 Jun 20. [5]. Terse P, et al. Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Int J Toxicol. 2014 Mar-Apr;33(2):75-85. [6]. Yu J, et al. DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest. 2018 Jun 1;128(6):2376-2388. [7]. Wang LX, et al. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumorspecific cytotoxic T lymphocyte responses. PLoS One. 2013 May 9;8(5):e62924. [8]. Quantitative determination of decitabine incorporation into DNA and its effect on mutation rates in human cancer cells. Nucleic Acids Res. 2014 Oct 29; 42(19): e152. |
Molecular Formula |
C8H12N4O4
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Molecular Weight |
228.21
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Exact Mass |
228.08586
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CAS # |
2353-33-5
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Appearance |
White to off-white solid
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LogP |
-1.2
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tPSA |
121Ų
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SMILES |
O=C1N([C@H]2O[C@H](CO)[C@@H](O)C2)C=NC(N)=N1
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InChi Key |
XAUDJQYHKZQPEU-KVQBGUIXSA-N
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InChi Code |
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
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Chemical Name |
4-amino-1-((2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one
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Synonyms |
5-Aza-2'-deoxycytidine; deoxyazacytidine; 5-aza-dCyd; Deoxycytidine; NSC127716; NSC 127716; NSC-127716; dezocitidine; Brand name: Dacogen. Abbreviations: 5AZA; DAC
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W:30mg/mL Solubility in Formulation 5: 10 mg/mL (43.82 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.3819 mL | 21.9096 mL | 43.8193 mL | |
5 mM | 0.8764 mL | 4.3819 mL | 8.7639 mL | |
10 mM | 0.4382 mL | 2.1910 mL | 4.3819 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02316028 | Completed | Drug: Decitabine | Liver Metastasis Colorectal Cancer |
Universitair Ziekenhuis Brussel | March 2014 | Phase 1 Phase 2 |
NCT05960773 | Recruiting | Drug: Decitabine/cedazuridine | Mesothelioma Malignant Mesothelioma (MM) |
National Cancer Institute (NCI) | January 31, 2024 | Phase 2 |
NCT05816356 | Recruiting | Drug: Decitabine Drug: Tetrahydrouridine |
Healthy | EpiDestiny, Inc. | March 24, 2023 | Phase 1 |
NCT04582604 | Recruiting | Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine |
Peripheral Blood Stem Cell Transplantation |
Chinese PLA General Hospital | September 1, 2020 | Phase 1 Phase 2 |