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.

＞98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

泽布拉林；2-嘧啶酮-B-核甙；NSC309132；4-Deoxyuridine

off-white solid

DMSO : 22.8 mg/mL (100 mM)；
water : 22.8 mg/mL (100 mM)

DNA methyltransferase；Cytidine deaminase

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.

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.

[1]. 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.

[2]. 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.

[3]. Cheng JC, et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst, 2003, 95(5), 399-409.

[4]. Cheng JC, et al. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2), 151-158.