Zebularine
Zebularine, a chemically stable cytidine analog containing a 2-(1H)-pyridimidinone ring, is an effective DNA methylation inhibitor which can act with DNA methyltransferases to form a covalent complex. It has been shown to cause demethylation and reactivation of a silenced and hypermethylated p16 gene. Zebularine is able to induce the myogenic phenotype in 10T1/2 cells, which is a phenomenon unique to DNA methylation inhibitors. zebularine can act as a pro-drug leading to inhibition of DNA methylation and gene activation in fungal and mammalian cells. It was the only slightly cytotoxic to T24 cells in vitro. Zebularine is stable in aqueous solution up to a pH of 12.
Reference
C.B. Yoo, J.C. Cheng and P.A. Jones. Zebularine: a new drug for epigenetic therapy. Biochemical Society Transactions. 2004; 32(6): 910 – 912.
Jonathan C. Cheng, Cindy B. Matsen, Felicidad A. Gonzales, Wei Ye, Sheldon Greer, Victor E. Marquez, Peter A. Jones, Eric U. Selker. Inhibition of DNA Methylation and Reactivation of Silenced Genes by Zebularine. Journal of the National Cancer Institute. 2003; 95(5): 399 – 409.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 228.2 |
| Cas No. | 3690-10-6 |
| Formula | C9H12N2O5 |
| Synonyms | NSC 309132 |
| Solubility | insoluble in EtOH; ≥50.7 mg/mL in H2O; ≥8.3 mg/mL in DMSO |
| Chemical Name | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one |
| SDF | Download SDF |
| Canonical SMILES | C1=CN(C(=O)N=C1)C2C(C(C(O2)CO)O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
10T1/2 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
30 μM; 24 hrs |
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Applications |
In 10T1/2 cells, Zebularine induced muscle cell formation. However, the 10T1/2 cells treated with Zebularine showed less muscle cell formation than those treated with either 5-Aza-CdR or 5-Aza-CR. |
| Animal experiment [1]: | |
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Animal models |
BALB/c nu/nu mice bearing EJ6 bladder cell xenografts |
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Dosage form |
500 or 1000 mg/kg; i.p. or p.o. |
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Applications |
In BALB/c nu/nu mice bearing EJ6 bladder cell xenografts, Zebularine (1000 mg/kg) significantly reduced tumor volumes when administered by intraperitoneal injection or by oral gavage. Moreover, Zebularine only showed slight cytotoxicity to tumor-bearing mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Cheng JC, Matsen CB, Gonzales FA, Ye W, Greer S, Marquez VE, Jones PA, Selker EU. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst. 2003 Mar 5;95(5):399-409. |
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| Description | Zebularine is a potent inhibitor of both DNA Methyltransferases and cytidine deaminase. | |||||
| Targets | DNA Methyltransferases | cytidine deaminase | ||||
| IC50 | 2 μM | |||||
Quality Control & MSDS
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Chemical structure
Related Biological Data
Related Biological Data
