TBB
(Synonyms: 4,5,6,7-四溴-1H-苯并三唑,NSC 231634; TBB (enzyme inhibitor);1H-Benzotriazole, 4,5,6,7-tetrabromo-) 目录号 : GC12181
TBB是一种细胞可渗透的ATP竞争性CK2抑制剂，对大鼠肝脏CK2的IC50为0.15μM。
Cas No.:17374-26-4
Sample solution is provided at 25 µL, 10mM.
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TBB is a cell-permeable and ATP-competitive CK2 inhibitor with an IC50 of 0.15μM for rat liver CK2[1]. TBB also inhibits three other kinases with less potency: CDK2 (IC50=15.6μM), phosphorylase kinase (IC50=8.7μM) and glycogen synthase kinase 3β (GSK3β) (IC50=11.2μM). All other kinases tested have IC50 values 50-fold greater than that for CK2[2]. TBB is commonly used for studying the role of CK2 in cell signal transduction and gene expression regulation, and can also be applied in the research of related diseases[3-5].
In vitro, treatment of PC-3 cells with 60μM TBB(24h) followed by a 24h period when cells were cultured without TBB, the viability was considerably lowered, and the time schedule-dependence of the effect was maintained when TBB was administered in combination with Camptothecin (CPT)[6].
In vivo, intraperitoneal injection of TBB (60mg/kg/day for 6 days) reduced retinal neovascularization by approximately 60% in the mouse oxygen-induced retinopathy (OIR) model, with minimal effects on the main vascular tree but marked suppression or elimination of neovascular tufts[7].
References:
[1] Pagano, M. A., Bain, J., Kazimierczuk, Z., Sarno, S., Ruzzene, M., Di Maira, G., Elliott, M., Orzeszko, A., Cozza, G., Meggio, F., & Pinna, L. A. (2008). The selectivity of inhibitors of protein kinase CK2: an update. The Biochemical journal, 415(3), 353–365.
[2] De Moliner, E., Brown, N. R., & Johnson, L. N. (2003). Alternative binding modes of an inhibitor to two different kinases. European journal of biochemistry, 270(15), 3174–3181.
[3] Sarno, S., Reddy, H., Meggio, F., Ruzzene, M., Davies, S. P., Donella-Deana, A., Shugar, D., & Pinna, L. A. (2001). Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 ('casein kinase-2'). FEBS letters, 496(1), 44–48.
[4] Chen, Z., Chen, Q., Huang, J., Gong, W., Zou, Y., Zhang, L., Liu, P., & Huang, H. (2018). CK2α promotes advanced glycation end products-induced expressions of fibronectin and intercellular adhesion molecule-1 via activating MRTF-A in glomerular mesangial cells. Biochemical pharmacology, 148, 41–51.
[5] Zwicker, F., Hauswald, H., Weber, K. J., Debus, J., & Huber, P. E. (2021). In Vivo Evaluation of Combined CK2 Inhibition and Irradiation in Human WiDr Tumours. In vivo (Athens, Greece), 35(1), 111–117.
[6] Orzechowska, E., Kozłowska, E., Staroń, K., & Trzcińska-Danielewicz, J. (2012). Time schedule-dependent effect of the CK2 inhibitor TBB on PC-3 human prostate cancer cell viability. Oncology reports, 27(1), 281–285.
[7] Ljubimov, A. V., Caballero, S., Aoki, A. M., Pinna, L. A., Grant, M. B., & Castellon, R. (2004). Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization. Investigative ophthalmology & visual science, 45(12), 4583–4591.
TBB是一种细胞可渗透的ATP竞争性CK2抑制剂，对大鼠肝脏CK2的IC50为0.15μM[1]。TBB对CDK2（IC50=15.6μM）、磷酸化酶激酶（IC50=8.7μM）和糖原合成酶激酶3β（GSK3β）（IC50=11.2μM）也有较弱的抑制作用。所有其他测试的激酶的IC50值均比CK2高50倍以上[2]。TBB常用于研究CK2在细胞信号转导和基因表达调控中的作用，也可用于相关疾病的研究[3-5]。
体外实验中，60μM TBB处理PC-3细胞24小时后，在无TBB条件下继续培养24小时，细胞活力显著降低；当TBB与抗癌药物CPT联合使用时，该时间依赖性效应依然存在[6]。
体内实验中，腹腔注射TBB（60mg/kg/天；连续6天）使小鼠氧诱导视网膜病变（OIR）模型的视网膜新生血管化程度降低约60%，对主血管树影响轻微，但显著抑制或完全消除了新生血管丛[7]。
| Cell experiment [1]: | |
Cell lines | PC-3 cells |
Preparation Method | PC-3 cells were cultured routinely in RPMI-1640 media, respectively, which were supplemented with 10% FBS, penicillin (100U/ml) and streptomycin (100µg/ ml) at 37˚C in a humidified atmosphere of 5% CO2. Cells were seeded at 5x104cells/well in 24-wells plates and cultured for 72h. TBB (final concentration 60µM), Camptothecin (CPT) (final concentration 5.8nM), 2-deoxyglucose (2-DG; final concentration 0.5mM) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (final concentration 13.3ng/ml) were added to the medium individually or in a combination for 24h. Then the medium with the agent was removed and the cells were cultured for another 24h in normal medium. After that, 500µl of MTT mixture (0.5mg/ml in medium without phenol red) was added to each well and incubated for an additional 1h at 37˚C. The formazan crystals were diluted in 250µl of DMSO. The absorbance was measured at 570nm. |
Reaction Conditions | 60μM; 24h |
Applications | TBB reduced the viability of PC-3 cells either alone or combined with anticancer agents CPT or TRAIL when a proper time schedule of the administration is applied. |
| Animal experiment [2]: | |
Animal models | C57BL/6J mice |
Preparation Method | Proliferative retinopathy in neonatal mice was induced in heterozygous C57BL/6J mice. Mice from the retinopathy group were placed in 75% oxygen at postnatal day 7 and maintained in these conditions with their nursing mothers for 5 days. These mice were then returned to normal air and maintained for another 5 days. Nor-moxic control mice were maintained in normal air for the same duration as test mice and under the same conditions of light cycle and temperature. For in vivo administration, the CK2 inhibitors emodin and TBB were dissolved in PBS (pH 7.2) with 20% polyethylene glycol 400 (PEG 400) and 2% Tween-80. This solvent did not elicit any animal tolerance problems, unlike ethanol or DMSO. Inhibitors were injected intraperitoneally in volumes of 50μL or less per mouse at doses of 15 to 30mg/kg body weight, twice daily from day 11 to day 17. Control mice were injected with PEG-Tween vehicle alone. At the end of the experiment, mice were euthanatized by intraperitoneal injection with tribromoethanol (0.1ml/g body weight).The eyes were enucleated and fixed in 4% paraformaldehyde in 0.1M phosphate buffer (pH 7.4) for 18 hours for further analysis. |
Dosage form | 30 to 60mg/kg/day for 6 days; i.p. |
Applications | TBB reduced retinal neovascularization by approximately 60% in the mouse OIR model with minimal effects on the main vascular tree but marked suppression or elimination of neovascular tufts. |
References: | |
| Cas No. | 17374-26-4 | SDF | |
| 别名 | 4,5,6,7-四溴-1H-苯并三唑,NSC 231634; TBB (enzyme inhibitor);1H-Benzotriazole, 4,5,6,7-tetrabromo- | ||
| 化学名 | 4,5,6,7-tetrabromo-2H-benzotriazole | ||
| Canonical SMILES | C1(=C(C2=NNN=C2C(=C1Br)Br)Br)Br | ||
| 分子式 | C6HBr4N3 | 分子量 | 434.71 |
| 溶解度 | ≥ 159.2 mg/mL in DMSO, ≥ 10.42 mg/mL in EtOH 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 | 2.3004 mL | 11.5019 mL | 23.0038 mL |
| 5 mM | 0.4601 mL | 2.3004 mL | 4.6008 mL |
| 10 mM | 0.23 mL | 1.1502 mL | 2.3004 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 | ||||||||||
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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，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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