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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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].
| Cell experiment [1]: | |
|
Cell lines |
OCI-AML3 cells |
|
Preparation Method |
Cells were treated with a specified concentration of DZNep for 24 h. |
|
Reaction Conditions |
DZNep (0/1.0 µM); 24 h |
|
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]: | |
|
Animal models |
Female nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice |
|
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. |
|
Dosage form |
1 mg/kg DZNep; i.p.; twice a week for 2 weeks |
|
Applications |
NOD/SCID mice treated with DZNep had significantly improved survival from AML caused by HL-60 cells. |
|
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. | |
| 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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet