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3-Deazaneplanocin A HCl

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Chemical Structure| 120964-45-6 同义名 : DZNep hydrochloride;3-Deazaneplanocin hydrochloride;2,3-DMMC;3-Deazaneplanocin A (hydrochloride);NSC 617989 HCl;DZNeP HCl;NSC 617989 hydrochloride;3-Deazaneplanocin A hydrochloride
CAS号 : 120964-45-6
货号 : A746301
分子式 : C12H15ClN4O3
纯度 : 99%+
分子量 : 298.726
MDL号 : MFCD18782644
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3个月-80°C:12个月
溶解度 :

H2O: 50 mg/mL(167.38 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • Histone Methyltransferase

    S-adenosylhomocysteine hydrolase, Ki:50 pM
描述 3-Deazaneplanocin A is a cyclopentanyl analog of 3-deazaadenosine that potently interferes with SAH, a component of the methionine cycle, which causes cellular SAH levels to increase, thus repressing the activity of S-adenosyl-l-methionine–dependent histone lysine methyltransferase activity[1]. Thus, the effect of 3-Deazaneplanocin A in inhibiting histone methylation is not specific to EZH2. Treatment with 5 μM of 3-Deazaneplanocin A for 72h led to a global decrease in most histone examined, including H3K27me3, H3K9me2, H3K79me3, H4K20me3, H3K4me3, H3K9me1, H3R2me2 and H3K27me1, with most reduction on H3K27me3 and H4K20me3, in MCF-7 cells, as well as slight decrease of EZH2[1]. Treatment with 5 µM 3-Deazaneplanocin A for 48 and 72h depletes EZH2 proteins as well as inhibits histone H3-K27 methylation, and induces apoptotic cell death in MCF-7 and HCT116 cells. 3-Deazaneplanocin A treatment removes the binding of PRC2 to their target genes and increases the binding of RNA Pol II, thus increases recruitment of RNA Pol II and transcriptional activation of these PRC2 target genes, such as FBXO32, LAMB3, PLAU, and PPP1R15A, in MCF-7 cells, MDA-MB-468, SK-BR-3 and T47D cell lines sensitive to DZNep-induced cell death[2]. Recently, it was found that 3-Deazaneplanocin A can enhance Oct4 expression in chemically induced pluripotent stem cells[3].
作用机制 Deazaneplanocin A is a cyclopentanyl analog of 3-deazaadenosine, thus functioning as a SAH hydrolase inhibitor of methyltransferases[1].
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 A549 cells Cytotoxic assay 72 h Cytotoxicity against human A549 cells assessed as inhibition of cell proliferation after 72 hrs by sulforhodamine B assay, IC50=1.4 μM. 26010585
human HCT116 cells Cytotoxic assay 72 h Cytotoxicity against human HCT116 cells assessed as inhibition of cell proliferation after 72 hrs by sulforhodamine B assay, IC50=0.26 μM. 26010585
human MDA-MB-231 cells Cytotoxic assay 72 h Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell proliferation after 72 hrs by sulforhodamine B assay， IC50=0.3 μM. 26010585
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.35mL

0.67mL

0.33mL

16.74mL

3.35mL

1.67mL

33.48mL

6.70mL

3.35mL
参考文献

[1]Miranda TB, Cortez CC, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther. 2009 Jun;8(6):1579-88.

[2]Tan J, Yang X, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 2007 May 1;21(9):1050-63. Epub 2007 Apr 16.

[3]Hou P, Li Y, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013 Aug 9;341(6146):651-4.

[4]Fiskus W, Wang Y, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood. 2009 Sep 24;114(13):2733-43.

[5]Sun F, Lee L, et al. Preclinical pharmacokinetic studies of 3-deazaneplanocin A, a potent epigenetic anticancer agent, and its human pharmacokinetic prediction using GastroPlus™. Eur J Pharm Sci. 2015 Sep 18;77:290-302.