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Chemical Structure| 3690-10-6 Chemical Structure| 3690-10-6

Structure of Zebularine
CAS No.: 3690-10-6

Chemical Structure| 3690-10-6

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Zebularine is a DNA methylation inhibitor which forms a covalent complex with DNA methyltransferases, it also inhibits cytidinedeaminase with Ki of 2 μM.

Synonyms: NSC309132; 4-Deoxyuridine; Pyrimidin-2-one beta-ribofuranoside

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Product Details of Zebularine

CAS No. :3690-10-6
Formula : C9H12N2O5
M.W : 228.20
SMILES Code : O=C1N=CC=CN1[C@H](O[C@@H]2CO)[C@H](O)[C@@H]2O
Synonyms :
NSC309132; 4-Deoxyuridine; Pyrimidin-2-one beta-ribofuranoside
MDL No. :MFCD04973699
InChI Key :RPQZTTQVRYEKCR-WCTZXXKLSA-N
Pubchem ID :100016

Safety of Zebularine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Zebularine

epigenetics
DNA

Isoform Comparison

Biological Activity

Target
  • DNA Methyltransferase

In Vitro:

Cell Line
Concentration Treated Time Description References
HaCaT cells 1 μg/mL 48 h To investigate the effect of Zebularine on the proliferation and cytotoxicity of HaCaT cells. Results showed that Zebularine slightly stimulated proliferation at low concentrations (0.1 and 1.0 μg/mL) but inhibited proliferation at higher concentrations. PMC6710911
46BR.1N cells 1 μg/mL 48 h To investigate the effect of Zebularine on the proliferation and cytotoxicity of 46BR.1N cells. Results showed that Zebularine slightly stimulated proliferation at low concentrations (0.1 and 1.0 μg/mL) but inhibited proliferation at higher concentrations. PMC6710911
Arabidopsis thaliana cells 20 µM 10 days Screening for mutants sensitive to Zebularine, revealing that SMC6B mutants are highly sensitive to Zebularine PMC10118267
Diabetic LEC 1–20 µM 24 h Zebularine treatment significantly increased Wnt-5a levels and stimulated wound healing in a dose-dependent manner, with a 1.6-fold increase by 24 h. PMC10474199
HL60 cells 50 or 100 µM 96 h To investigate the effect of Zebularine on HL60 cell differentiation, results showed that Zebularine significantly increased the expression of the CD11b differentiation marker. PMC7563846

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Unilateral ureteral obstruction model Intraperitoneal injection 225 mg/kg Once daily for 3 or 7 days Zebularine significantly attenuated renal tubulointerstitial fibrosis and inflammation induced by unilateral ureteral obstruction. PMC9697081
BALB/c mice Oral cancer model Oral 1 mg/ml Daily, starting from PID 4 To evaluate the analgesic effect of Zebularine in an oral cancer model, results showed that Zebularine significantly reduced tumor growth and produced mechanical and thermal antinociception. PMC4294581
Mice Ear pinna injury model Intraperitoneal injection 1000 mg/kg 7 injections over 10 days To investigate the effect of Zebularine on ear pinna wound regeneration in mice. Results showed that Zebularine significantly promoted ear hole repair, with the mean hole area decreasing by 83.2 ± 9.4% in treated mice compared to 43.6 ± 15.4% in control mice. PMC6710911
Mice MMTV-PyMT transgenic mice Drinking water 5 mg/mL Daily, for 48 days Zebularine significantly delayed mammary tumor growth, and after 48 days of treatment, the tumors were predominantly necrotic, with a high apoptotic index observed by TUNEL assay as early as 13 days following treatment. PMC7457145
Mice Experimental autoimmune uveitis (EAU) model Intraperitoneal injection 10 µg/g Once daily for 7 consecutive days To evaluate the effect of zebularine on intraocular inflammation in EAU mice, results showed that zebularine significantly alleviated intraocular inflammation and retinal tissue damage. PMC6706956

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.38mL

0.88mL

0.44mL

21.91mL

4.38mL

2.19mL

43.82mL

8.76mL

4.38mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

[1]Lemaire M, Momparler LF, et al. Inhibition of cytidine deaminase by zebularine enhances the antineoplastic action of 5-aza-2'-deoxycytidine. Cancer Chemother Pharmacol. 2009 Feb;63(3):411-6.

[2]Zhou L, Cheng X, et al. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol. 2002 Aug 23;321(4):591-9.

[3]Sabatino MA, Geroni C, et al. Zebularine partially reverses GST methylation in prostate cancer cells and restores sensitivity to the DNA minor groove binder brostallicin. Epigenetics. 2013 Jun;8(6):656-65.

[4]Holleran JL, Parise RA, et al. Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyltransferase inhibitor, zebularine. Clin Cancer Res. 2005 May 15;11(10):3862-8.

[5]Fulkerson CM, Dhawan D, et al. Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs. Vet Comp Oncol. 2017 Mar;15(1):226-236.

[6]Gravina GL, Festuccia C, Marampon F, Popov VM, Pestell RG, Zani BM, Tombolini V. Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation. Mol Cancer. 2010 Nov 25;9:305.

[7]Gros C, Chauvigné L, Poulet A, Menon Y, Ausseil F, Dufau I, Arimondo PB. Development of a universal radioactive DNA methyltransferase inhibition test for high-throughput screening and mechanistic studies. Nucleic Acids Res. 2013 Oct;41(19):e185.

[8]Nakamura K, Nakabayashi K, Htet Aung K, Aizawa K, Hori N, Yamauchi J, Hata K, Tanoue A. DNA methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death through alteration of DNA methylation status. PLoS One. 2015 Mar 23;10(3):e0120545.

[9]Tan W, Zhou W, Yu HG, Luo HS, Shen L. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 2013 Jan 4;430(1):250-5.

[10]Hurd PJ, Whitmarsh AJ, Baldwin GS, Kelly SM, Waltho JP, Price NC, Connolly BA, Hornby DP. Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J Mol Biol. 1999 Feb 19;286(2):389-401.

 

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