3-Deazaneplanocin A (DZNep) hydrochloride
(Synonyms: 3-去氮腺嘌呤A盐酸盐; DZNep hydrochloride; NSC 617989 hydrochloride; 3-Deazaneplanocin hydrochloride) 目录号 : GC17907
3-Deazaneplanocin A (DZNep) hydrochloride 是一种腺苷类似物，是一种竞争性 S-腺苷高半胱氨酸水解酶抑制剂，在无细胞试验中的 Ki 为 50 pM。
Cas No.:120964-45-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
OCI-AML3 cells |
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Preparation Method |
Cells were treated with a specified concentration of DZNep for 24 h. |
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Reaction Conditions |
DZNep (0/1.0 µM); 24 h |
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Applications |
Treatment of OCI-AML3 cells with DZNep (1.0 µM) resulted in a significant increase in accumulation of cells in the G0/G1 phase with a concomitant decrease in the number of cells in S phase and G2/M phases of the cell cycle. |
| Animal experiment [2]: | |
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Animal models |
Female nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice |
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Preparation Method |
HL-60 cells (5 million) were injected into the tail vein of mice. The following treatments were administered in cohorts of 7 mice for each treatment: vehicle alone, 1 mg/kg DZNep, 10 mg/kg PS, and DZNep plus PS. Treatments were initiated on day 7. DZNep was administered twice per week intraperitoneally for 2 weeks, and then discontinued. |
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Dosage form |
1 mg/kg DZNep; i.p.; twice a week for 2 weeks |
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Applications |
NOD/SCID mice treated with DZNep had significantly improved survival from AML caused by HL-60 cells. |
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References: [1]. Tseng CK, Marquez VE, Fuller RW, Goldstein BM, Haines DR, McPherson H, Parsons JL, Shannon WM, Arnett G, Hollingshead M, et al. Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities. J Med Chem. 1989 Jul;32(7):1442-6. doi: 10.1021/jm00127a007. PMID: 2544721. | |
3-Deazaneplanocin A (DZNep) hydrochloride is an adenosine analogue and is a competitive S-adenosylhomocysteine hydrolase inhibitor with a Ki of 50 pM in cell-free tests.This results in the intracellular accumulation of AdoHcy, which leads to inhibition of the S-adenosyl-l-methionine dependent KMTase activity[1-2,5].3-Deazaneplanocin A (DZNep) hydrochloride has also been shown to inhibit the activity of the methyltransferases, resulting in undermethylation of mRNAs[3].
3-Deazaneplanocin A (DZNep) hydrochloride (100-750 nmol/L; 48 hours) treatment induces cell-cycle arrest and apoptosis, and markedly reduces clonogenic survival of AML cells[4]. 3-Deazaneplanocin A (DZNep) hydrochloride was reported to deplete the expression levels of the PRC2 complex in breast cancer cells with concomitant loss of 3Me H3K27 mark and derepression of epigenetically silenced targets[6]. 3-Deazaneplanocin A (DZNep) hydrochloride(10-6M-10-5M ;2 days)displayed excellent antiviral activity in cell culture against vesicular stomatitis, parainfluenza type 3, yellow fever, and vaccinia viruses[1].
3-Deazaneplanocin A (DZNep) hydrochloride (1 mg/kg; i.p.; 2 weeks) and panobinostat induced apoptosis of AML cells and significantly improved the survival rate of non-obese diabetic/severely immunodeficient mice with HL-60 leukemia [4]. 3-Deazaneplanocin A (DZNep)(i.p.; 0.5-1.5 mg/kg/d; 2 weeks)can significantly reduce the incidence of leishmania infection in skin of inbred BALB/c mice induced by L. b. guyanensis inoculation [7].
References:
[1]. Glazer RI, Hartman KD, et,al.3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun. 1986 Mar 13;135(2):688-94. doi: 10.1016/0006-291x(86)90048-3. PMID: 3457563.
[2]. Bray M, Driscoll J, et,al.Treatment of lethal Ebola virus infection in mice with a single dose of an S-adenosyl-L-homocysteine hydrolase inhibitor. Antiviral Res. 2000 Feb;45(2):135-47. doi: 10.1016/s0166-3542(00)00066-8. PMID: 10809022.
[3]. Jiang X, Tan J, et,al. DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 2008 Jun;13(6):529-41. doi: 10.1016/j.ccr.2008.04.019. PMID: 18538736; PMCID: PMC2577847.
[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. doi: 10.1182/blood-2009-03-213496. Epub 2009 Jul 28. PMID: 19638619; PMCID: PMC2756128.
[5]. Tseng CK, Marquez VE, Fuller RW, Goldstein BM, Haines DR, McPherson H, Parsons JL, Shannon WM, Arnett G, Hollingshead M, et al. Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities. J Med Chem. 1989 Jul;32(7):1442-6. doi: 10.1021/jm00127a007. PMID: 2544721.
[6]. 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. doi: 10.1101/gad.1524107. Epub 2007 Apr 16. PMID: 17437993; PMCID: PMC1855231.
[7]. Avila JL, Avila A, et,al.Specific inhibitory effect of 3-deazaneplanocin A against several Leishmania mexicana and L. braziliensis strains. Am J Trop Med Hyg. 1997 Oct;57(4):407-12. doi: 10.4269/ajtmh.1997.57.407. PMID: 9347954.
3-Deazaneplanocin A (DZNep) hydrochloride 是一种腺苷类似物，是一种竞争性 S-腺苷高半胱氨酸水解酶抑制剂，在无细胞试验中的 Ki 为 50 pM。这会导致 AdoHcy 在细胞内积聚，从而抑制S-腺苷-l-甲硫氨酸依赖性 KMTase 活性[1-2,5].3-Deazaneplanocin A (DZNep) 盐酸盐也被证明可以抑制甲基转移酶的活性，导致甲基化不足mRNAs[3].
3-Deazaneplanocin A (DZNep) 盐酸盐（100-750 nmol/L；48 小时）处理可诱导细胞周期停滞和细胞凋亡，并显着降低 AML 细胞的克隆形成存活率[4]。据报道，3-Deazaneplanocin A (DZNep) 盐酸盐会降低乳腺癌细胞中 PRC2 复合物的表达水平，同时会导致 3Me H3K27 标记缺失和表观遗传沉默靶标的去阻遏[6]。 3-Deazaneplanocin A (DZNep) hydrochloride（10-6M-10-5M ;2 天）在细胞培养中对水泡性口炎、副流感 3 型、黄热病和痘苗病毒表现出优异的抗病毒活性[1].
3-Deazaneplanocin A (DZNep) 盐酸盐（1 mg/kg；i.p.；2 周）和帕比司他诱导 AML 细胞凋亡，并显着提高患有 HL-60 白血病的非肥胖糖尿病/严重免疫缺陷小鼠的存活率 <支持>[4]。 3-Deazaneplanocin A (DZNep)(i.p.; 0.5-1.5 mg/kg/d; 2 weeks)可显着降低L. b.诱导的近交BALB/c小鼠皮肤利什曼原虫感染的发生率。圭亚那接种[7].
| Cas No. | 120964-45-6 | SDF | |
| 别名 | 3-去氮腺嘌呤A盐酸盐; DZNep hydrochloride; NSC 617989 hydrochloride; 3-Deazaneplanocin hydrochloride | ||
| 化学名 | (1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol;hydrochloride | ||
| Canonical SMILES | C1=CN=C(C2=C1N(C=N2)C3C=C(C(C3O)O)CO)N.Cl | ||
| 分子式 | C12H14N4O3.HCl | 分子量 | 298.73 |
| 溶解度 | ≥ 14.9mg/mL in DMSO, ≥ 18.32 mg/mL in Water with ultrasonic | 储存条件 | Store at -20°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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3475 mL | 16.7375 mL | 33.475 mL |
| 5 mM | 0.6695 mL | 3.3475 mL | 6.695 mL |
| 10 mM | 0.3348 mL | 1.6738 mL | 3.3475 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Epigenetics in NAFLD/NASH: Targets and therapy
Recently non-alcoholic fatty liver disease (NAFLD) has grabbed considerable scientific attention, owing to its rapid increase in prevalence worldwide and growing burden on end-stage liver diseases. Metabolic syndrome including obesity, diabetes, and hypertension poses a grave risk to NAFLD etiology and progression. With no drugs available, the mainstay of NAFLD management remains lifestyle changes with exercise and dietary modifications. Nonselective drugs such as metformin, thiazolidinediones (TZDs), ursodeoxycholic acid (UDCA), silymarin, etc., are also being used to target the interrelated pathways for treating NAFLD. Considering the enormous disease burden and the unmet need for drugs, fresh insights into pathogenesis and drug discovery are required. The emergence of the field of epigenetics offers a convincing explanation for the basis of lifestyle, environmental, and other risk factors to influence NAFLD pathogenesis. Therefore, understanding these epigenetic modifications to target the primary cause of the disease might prove a rational strategy to prevent the disease and develop novel therapeutic interventions. Apart from describing the role of epigenetics in the pathogenesis of NAFLD as in other reviews, this review additionally provides an elaborate discussion on exploiting the high plasticity of epigenetic modifications in response to environmental cues, for developing novel therapeutics for NAFLD. Besides, this extensive review provides evidence for epigenetic mechanisms utilized by several potential drugs for NAFLD.
Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride
Duchenne muscular dystrophy (DMD) is a severe muscle disorder characterised by mutations in the DMD gene. Recently, we have completed a phase I study in Japan based on systemic administration of the morpholino antisense that is amenable to exon-53 skipping, successfully. However, to achieve the effective treatment of DMD, in vitro assays on patient muscle cells to screen drugs and patient eligibility before clinical trials are indispensable. Here, we report a novel MYOD1-converted, urine-derived cells (UDCs) as a novel DMD muscle cell model. We discovered that 3-deazaneplanocin A hydrochloride, a histone methyltransferase inhibitor, could significantly promote MYOGENIN expression and myotube differentiation. We also demonstrated that our system, based on UDCs from DMD patients, could be used successfully to evaluate exon-skipping drugs targeting DMD exons including 44, 50, 51, and 55. This new autologous UDC-based disease modelling could lead to the application of precision medicine for various muscle diseases.
Publisher Correction: Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Epigenetic Modifications with DZNep, NaBu and SAHA in Luminal and Mesenchymal-like Breast Cancer Subtype Cells
Background/aim: Numerous studies have shown that breast cancer and epigenetic mechanisms have a very powerful interactive relation. The MCF7 cell line, representative of luminal subtype and the MDA-MB 231 cell line representative of mesenchymal-like subtype were treated respectively with a Histone Methyl Transferase Inhibitors (HMTi), 3-Deazaneplanocin hydrochloride (DZNep), two histone deacetylase inhibitors (HDACi), sodium butyrate (NaBu), and suberoylanilide hydroxamic acid (SAHA) for 48 h.
Materials and methods: Chromatin immunoprecipitation (ChIP) was used to observe HDACis (SAHA and NaBu) and HMTi (DZNep) impact on histones and more specifically on H3K27me3, H3K9ac and H3K4ac marks with Q-PCR analysis of BRCA1, SRC3 and P300 genes. Furthermore, the HDACi and HMTi effects on mRNA and protein expression of BRCA1, SRC3 and P300 genes were checked. In addition, statistical analyses were used.
Results: In the MCF7 luminal subtype with positive ER, H3k4ac was significantly increased on BRCA1 with SAHA. On the contrary, in the MDA-MB 231 breast cancer cell line, representative of mesenchymal-like subtype with negative estrogen receptor, HDACis had no effect. Also, DZNEP decreased significantly H3K27me3 on BRCA1 in MDA-MB 231. Besides, on SRC3, a significant increase for H3K4ac was obtained in MCF7 treated with SAHA. And DZNEP had no effect in MCF7. Also, in MDA-MB 231 treated with DZNEP, H3K27me3 significantly decreased on SRC3 while H3K4ac was significantly increased in MDA-MB-231 treated with SAHA or NaBu for P300.
Conclusion: Luminal and mesenchymal-like breast cancer subtype cell lines seemed to act differently to HDACis (SAHA and NaBu) or HMTi (DZNEP) treatments.
Exon Skipping in Directly Reprogrammed Myotubes Obtained from Human Urine-Derived Cells
Duchenne muscular dystrophy (DMD), a progressive and fatal muscle disease, is caused by mutations in the DMD gene that result in the absence of dystrophin protein. To date, we have completed an investigator-initiated first-in-human study at the National Center of Neurology and Psychiatry based on the systemic injection of the morpholino oligonucleotides which are prone to exon-53 skipping. For the effective treatment of DMD, in vitro testing with myoblasts derived from DMD patients to screen drugs and assess patient eligibility before undertaking clinical trials is thought to be essential. Very recently, we reported a new MYOD1-converted urine-derived cell (UDC) treated with the histone methyltransferase inhibitor (3-deazaneplanocin A hydrochloride), as a cellular model of DMD. The new autologous UDC might show phenocopy of the disease-specific phenotypes of DMD, leading to the application of precision medicine in a variety of muscle-related diseases. In this article, we describe a detailed protocol for efficient modelling of DMD muscle cells using MYOD1-converted UDCs along with reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry to evaluate the restoration of dystrophin mRNA and protein levels after exon skipping.