For research use only. Not Intended for Therapeutic Use!
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Zebularine(NSC309132; 4-Deoxyuridine) is a DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases, also inhibits cytidinedeaminase with Ki of 2 μM.
Target: DNA methyltransferase
in vitro: Zebularine is shown to form a tight, covalent complex with bacterial methyltransferases . Zebularine is a cytidine analogue containing a 2-(1H)-pyrimidinone ring, originally synthesized as a cytidine deaminase inhibitor . 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 .
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 .
. Zhou L, et al. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol, 2002, 321(4), 591-599.
. Lemaire M, et al. Inhibition of cytidine deaminase by zebularine enhances the antineoplastic action of 5-aza-2/'-deoxycytidine. Cancer Chemother Pharmacol, 2009, 63(3), 411-416.
. Cheng JC, et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst, 2003, 95(5), 399-409.
. Cheng JC, et al. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2), 151-158.