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, after 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]。