Zebularine
(Synonyms: 2-嘧啶酮-B-核甙,NSC 309132) 目录号 : GC12153
Zebularine是一种缺失4-氨基基团的胞苷类似物，作为DNA甲基转移酶抑制剂可抑制DNA甲基化。
Cas No.:3690-10-6
Sample solution is provided at 25 µL, 10mM.
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Zebularine, a cytidine lacking the 4-amino group, is a DNMT inhibitor that inhibits DNA methylation[1]. Zebularine can cause DNA demethylation and enhance cGAS-STING pathway activity, leading to accumulation of DNA fragments in the cytoplasm[2]. Zebularine has been widely used in cell models to inhibit tumor growth and alter cancer cell gene expression[3].
In vitro, Zebularine treatment for 24 hours significantly inhibited the viability of HCCLM3, MHCC97H, and MHCC97L cells with IC50 values of 56.75µM, 59.72µM, and 64.93µM, respectively[4]. Treatment of MDA-MB-231 cells with 200µM Zebularine for 96 hours significantly inhibited cell proliferation, induced S-phase arrest, and resulted in decreased expression of cyclins B and D[5]. Treatment of A549 cells with 100µM Zebularine for 72h induced apoptosis, accompanied by loss of mitochondrial membrane potential, decrease of Bcl-2, increase of Bax and p53, and activation of caspase-3 and caspase-8[6].
In vivo, Zebularine treatment via oral administration at a dose of 100mg/kg every four days for 20 days significantly inhibited tumor growth in the BGC823 cell xenograft mouse model[7]. Daily intraperitoneal injection of Zebularine (225mg/kg) for 7 days reduced the fibrotic lesion area and inflammatory response in the kidney in a mouse model of unilateral ureteral obstruction (UUO)[8].
References:
[1] Champion C, Guianvarc'h D, Sénamaud-Beaufort C, et al. Mechanistic insights on the inhibition of c5 DNA methyltransferases by zebularine[J]. PloS one, 2010, 5(8): e12388.
[2] Lai J, Fu Y, Tian S, et al. Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice[J]. Molecular Therapy, 2021, 29(5): 1758-1771.
[3] Cheng J C, Yoo C B, Weisenberger D J, et al. Preferential response of cancer cells to zebularine[J]. Cancer cell, 2004, 6(2): 151-158.
[4] Sanaei M, Kavoosi F. Effect of zebularine on apoptotic pathways in hepatocellular carcinoma cell lines[J]. International Journal of Preventive Medicine, 2023, 14(1): 63.
[5] Billam M, Sobolewski M D, Davidson N E. Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells[J]. Breast cancer research and treatment, 2010, 120(3): 581-592.
[6] You B R, Park W H. Zebularine inhibits the growth of A549 lung cancer cells via cell cycle arrest and apoptosis[J]. Molecular Carcinogenesis, 2014, 53(11): 847-857.
[7] Tan W, Zhou W, Yu H, et al. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo[J]. Biochemical and biophysical research communications, 2013, 430(1): 250-255.
[8] Koh E S, Kim S, Son M, et al. The protective effect of zebularine, an inhibitor of DNA methyltransferase, on renal tubulointerstitial inflammation and fibrosis[J]. International Journal of Molecular Sciences, 2022, 23(22): 14045.
Zebularine是一种缺失4-氨基基团的胞苷类似物，作为DNA甲基转移酶抑制剂可抑制DNA甲基化[1]。Zebularine通过诱导DNA去甲基化并增强cGAS-STING通路活性，导致细胞质中DNA片段积累[2]，Zebularine已广泛应用于细胞模型中抑制肿瘤生长及改变癌细胞基因表达[3]。
在体外，Zebularine处理24小时能显著抑制HCCLM3、MHCC97H和MHCC97L细胞活力，IC50值分别为56.75µM、59.72µM和64.93µM[4]。使用200µM的Zebularine处理MDA-MB-231细胞96小时，可显著抑制细胞增殖，诱导S期阻滞，并降低细胞周期蛋白B和D的表达[5]。用100µM的Zebularine处理A549细胞72小时，能诱导细胞凋亡，伴随线粒体膜电位丧失、Bcl-2下调、Bax和p53上调，以及caspase-3和caspase-8的激活[6]。
在体内，每四天口服100mg/kg剂量的Zebularine连续20天，可显著抑制BGC823细胞异种移植瘤小鼠模型的肿瘤生长[7]。在单侧输尿管梗阻（UUO）小鼠模型中，每天腹腔注射225mg/kg剂量的Zebularine 7天可减少肾脏纤维化病变面积和炎症反应[8]。
| Cell experiment [1]: | |
Cell lines | HCCLM3 cells |
Preparation Method | HCCLM3 cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and antibiotics (0.1mg/ml streptomycin and 100U/ml penicillin) at 37°C and 5% CO2 for 24 hours. Subsequently, all HCCLM3 cells were seeded in 96-well plates (3×105 cells per well). After 1 day, the medium was removed, and medium containing different concentrations of Zebularine (0, 10, 25, 50, 75, and 100μM) was added, while the control group was treated with 0.05% DMSO. After 24 hours of treatment with Zebularine, MTT solution (5mg/ml) was added to each well and incubated at 37°C for 4 hours. Subsequently, absorbance was measured at a wavelength of 570nm using a microplate reader. |
Reaction Conditions | 0, 10, 25, 50, 75, and 100μM; 24h |
Applications | Zebularine treatment inhibited the cell viability of HCCLM3 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female BALB/c nude mice |
Preparation Method | BGC823 cells were injected into the flank of BALB/c nude mice (female, 4-6 weeks of age) and maintained under specific pathogen-free (SPF) conditions. Mice were randomly divided into two groups: a control group and an experimental group (100mg/kg; p.o). Each group contained five nude mice (at least six tumors per group; 1-2 nude mice per group were randomly sacrificed and used to establish the time course of expression). When tumor volume reached 100-150mm3, nude mice were treated by gavage with Zebularine (dissolved in 0.45% saline) every 4 days for 20 days. The control group was given 0.45% normal saline by gavage every 4 days for 20 days. Tumor growth was monitored by measuring tumor volume (TV), which was calculated using the formula: TV (mm3) = width2(mm2)×length(mm)/2. |
Dosage form | 100mg/kg; every four days for 20 days; p.o. |
Applications | Zebularine treatment significantly reduced tumor xenograft growth in mice. |
References: | |
| Cas No. | 3690-10-6 | SDF | |
| 别名 | 2-嘧啶酮-B-核甙,NSC 309132 | ||
| 化学名 | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one | ||
| Canonical SMILES | C1=CN(C(=O)N=C1)C2C(C(C(O2)CO)O)O | ||
| 分子式 | C9H12N2O5 | 分子量 | 228.2 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 14 mg/ml,Ethanol: 0.25 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at 2-8°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.3821 mL | 21.9106 mL | 43.8212 mL |
| 5 mM | 876.4 μL | 4.3821 mL | 8.7642 mL |
| 10 mM | 438.2 μL | 2.1911 mL | 4.3821 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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