切换导航
关闭
  • 菜单
  • Setting

DMAT

 
Catalog No.
A3368
CK2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 727.00
现货
10mg
¥ 636.00
现货
50mg
¥ 2,181.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

A

背景

IC50 value: 0.13uM. DMAT also displays submicromolar IC50 values with almost all of the other kinases with special reference to PKD1, PIM3 and PIM1[3]. Protein kinase CK2 is involved in cell proliferation and survival, and found overexpressed in virtually all types of human cancer, including breast cancer. We demonstrate that inhibition of CK2 with 2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole (DMAT), a potent and specific CK2 inhibitor, results in caspase-mediated killing of human breast cancer cells with acquired resistance to antiestrogens [1]. In vitro:. Treatment with DMAT decreases the secretion of aldosterone, dehydroepiandrosterone sulfate, and androstendione in H295R human adrenocortical cancer cell line and results in an accumulation of 17-OH-progesterone. Cell growth as measured by the MTT and 5-bromo-2'-deoxyuridine incorporation assays is inhibited, and cell cycle analysis has revealed a slight induction of apoptosis[2]. PIM1 is also inhibited by DMAT by a mechanism which is competitive with respect to ATP. However, IC50 determinations at increasing ATP concentration denote weak competition by ATP which, at almost physiological concentration (0.6 mM), causes only a 5.3-fold decrease in DMAT inhibition, as compared with 1 μM ATP concentration, whereas in the same range of ATP concentration the IC50 with CK2 increases 22.1-fold, doubling the value calculated with PIM1 (1.2 μM) [3]. in vivo: Similar to Sorafenib, DMAT interfered with NFκB activation and Wnt-signaling. Of the kinases inhibited by DMAT at almost equimolar IC50, CK2 and PIM-3 were found to be over-expressed or more active in hepatoma cells and human HCC tissue. Knockdown of PIM-3 or CK2 by shRNA revealed that both kinases are important for hepatoma cell proliferation and survival [4]. DMAT, might represent a promising therapeutic approach in future HCC therapy. Clinical trial: Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene[3].

文献引用

化学属性

Physical AppearanceA solid
StorageStore at -20°C
M.Wt476.79
Cas No.749234-11-5
FormulaC9H7Br4N3
SynonymsCasein kinase II Inhibitor;CK2 Inhibitor
Solubility≥23.85 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
Chemical Name4,5,6,7-tetrabromo-N,N-dimethyl-1H-benzimidazol-2-amine
SDFDownload SDF
Canonical SMILESCN(C)C1=NC2=C(N1)C(=C(C(=C2Br)Br)Br)Br
运输条件 蓝冰运输或根据您的需求运输。
一般建议不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。

试验操作

细胞实验 [1]:

细胞系

人源多能肾上腺皮质细胞系H295R (CRL-2128)

溶解方法

在DMSO中的溶解度>23.9mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月

反应时间

DMAT溶解于96%乙醇和无类血清的培养基中,终浓度为10-4–10-10 M,72 h

应用

DMAT的使用减少了醛固酮,脱氢表雄酮硫酸盐,雄烯二酮的分泌,导致17-羟孕酮的积累。细胞生长被抑制,并且细胞周期分析显示了轻微的细胞凋亡的诱导。

动物实验[2]:

动物模型

6-8周携带人源肝癌细胞HepG2异种移植物的雄性NMRI小鼠

剂量

500 μg/kg 溶解于DMSO/PBS混合溶液,每日使用,10天,腹腔注射

应用

在带有异种移植瘤的模型体内,DMAT的使用通过干扰肿瘤细胞增殖来降低肿瘤生长。DMAT通过干扰NFκB和Wnt信号通路来减少HCC(肝细胞癌)生长。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Lawnicka H1, Kowalewicz-Kulbat M, et al, Anti-neoplastic effect of protein kinase CK2 inhibitor, 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), on growth and hormonal activity of human adrenocortical carcinoma cell line (H295R) in vitro. Cell Tissue Res. 2010 May;340(2):371-9. doi: 10.1007/s00441-010-0960-1. Epub 2010 Apr 6.

[2]. Sass G1, Klinger N, et al, Inhibition of experimental HCC growth in mice by use of the kinase inhibitor DMAT. Int J Oncol. 2011 Aug;39(2):433-42. doi: 10.3892/ijo.2011.1037. Epub 2011 May 10.

质量控制

化学结构

DMAT

相关生物数据

DMAT

相关生物数据

DMAT

相关生物数据

DMAT