product name Zebularine
Description: Zebularine is a DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases, also inhibits cytidinedeaminase with Ki of 2 μM in a cell-free assay. Chemically, zebularine is a stable cytidine analog containing a 2-(1H)-pyridimidinone ring. 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.
References:J Mol Biol. 2002 Aug 23;321(4):591-9; Cancer Chemother Pharmacol. 2009 Feb;63(3):411-6.
228.2
Formula
C9H12N2O5
CAS No.
3690-10-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 46 mg/mL (201.6 mM)
Water: 46 mg/mL (201.6 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Saline: 30 mg/mL
Synonyms
NSC 309132
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19410950
| In Vitro |
In vitro activity: Zebularine is a cytidine analogue containing a 2-(1H)-pyrimidinone ring, originally synthesized as a cytidine deaminase inhibitor. Zebularine is shown to form a tight, covalent complex with bacterial methyltransferases. In N. crassa, zebularine inhibits DNA methylation and reactivates a gene previously silenced by methylation. Zebularine is a global inhibitor of DNA methylation, similar to 5-Aza-CR, rather than a selective inhibitor. Zebularine induces the myogenic phenotype in 10T1/2 cells, which is a phenomenon unique to DNA methylation inhibitors. Zebularine reactivates a silenced p16 gene and demethylates its promoter region in T24 bladder carcinoma cells. Zebularine is only slightly cytotoxic to T24 cells. Zebularine is preferentially incorporated into DNA and exhibits greater cell growth inhibition and gene expression in cancer cell lines compared to normal fibroblasts. In addition, zebularine preferentially depletes DNA methyltransferase 1 (DNMT1) and induces expression of cancer-related antigen genes in cancer cells relative to normal fibroblasts. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Zebularine is only slightly cytotoxic to tumor-bearing mice (average maximal weight change in mice treated with 1000 mg/kg zebularine = 11% [95% CI = 4% to 19%]). Compared with those in control mice, tumor volumes are statistically significantly reduced in mice treated with high-dose zebularine administered by intraperitoneal injection or by oral gavage. |
| Animal model | Male BALB/c nu/nu mice |
| Formulation & Dosage | Dissolved in 0.45% saline; 500 mg/kg, 1000 mg/kg; i.p. and p.o. |
| References | FASEB J. 2000 Nov;14(14):2339-44; Cancer Res. 2010 Aug 1;70(15):6268-76. |
