Zebularine

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Chemical Structure| 3690-10-6 同义名 : NSC309132;4-Deoxyuridine;Pyrimidin-2-one beta-ribofuranoside;Pyrimidin-2-one ribonucleoside
CAS号 : 3690-10-6
货号 : A162514
分子式 : C9H12N2O5
纯度 : 98%
分子量 : 228.202
MDL号 : MFCD04973699
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(460.12 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 50 mg/mL(219.1 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • DNA Methyltransferase
描述 The DNA methyltransferase (DNMT) family are enzymes that can mediate the DNA methylation. Inhibiting the DNMTs have shown particular promise in reducing the formation of tumors[6]. Zebularine is a second-generation inhibitor of DNMT with IC50 value of 95 nM on DNMT1[7]. The TFK-1 and HuCCT1 cells were treated with zebularine from 100 - 1000 µM for 72 hours. The cell viability was significantly reduced in a dose dependent manner measured by WST assay. The protein expression level of DNMT1, DNMT3a, DNMT3b examined by western blotting assay was significantly inhibited for both cell lines at concentration of 400 µM and above[8]. BALB/c nude mice with tumor were treated with 10, 50 and 100 mg/kg zebularine via oral gavage in a solution of 0.45% saline every four days for 20 days. The tumor growth was reduced in a dose dependent manner and the cell death in the tumor mass via apoptosis was induced by the treatement of zebularine as measured by the TUNEL assay[9].
作用机制 Zebularine could form tight covalent complexes between the DNMT proteins and zebularine-substitute DNA[10].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human HCT15 cells 100 μM Function assay 8 days Induction of p16 gene expression in human HCT15 cells at 100 uM after 8 days by real time PCR in presence of 100 mM thymidine 19006382
human T24 cells 100 μM Function assay 8 days Induction of p16 gene expression in human T24 cells at 100 uM after 8 days by real time PCR in presence of 100 mM thymidine 19006382
实验方案
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
参考文献

[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.