TBBz has been used as a CK2 inhibitor in HeLa cells and rat septal neurons.
A selective ATP-competitive inhibitor of protein kinase CK2 from such divergent sources as yeast, rat liver, Neurospora erassa and Candida tropicalis, with Ki values in the range of 0.5-1uM. It is virtually inactive against PKA, PKC, and a very weak inhibitor of protein kinase CK1.
ki: 0.5-1 μm4,5,6,7-tetrabromobenzimidazole is a ck2 inhibitor.casein kinase 2 (ck2), a constitutive protein kinase involved in many signal transduction pathways, is known to be able to negatively regulate apoptosis, and its activity is increased in various proliferating tissues and tumors.
TBBz is a cell-permeable Casein Kinase-2 (CK2) inhibitor. CK2 inhibitors, 4,5,6,7-tetrabromobenzotriazole (TBBt, Sigma Cat. # T0826) and rabromobenzimidazole (TBBz), the latter of which was shown to discriminate between different molecular forms of CK2 in yeast. TBBt, with a pK(a) ~5, exists in solution at physiological pH almost exclusively (>99%) as the monoanion; whereas TBBz, with a pKa ~9, is predominantly (>95%) in the neutral form, both of obvious relevance to their modes of binding. In vitro, TBBt inhibits different forms of CK2 with Ki values ranging from 80 to 210 nM. TBBz discriminates better between CK2 forms, with Ki values ranging from 70-510 nM. TBBz is more effective than TBBt in inducing apoptosis and to a lesser degree, necrosis in transformed human cell lines. Dvelopment of shRNA strategies for the selective knockdown of the CK2α and CK2α′ isoforms reinforces the foregoing results, indicating that inhibition of CK2 leads to attenuation of proliferation.
previous study found that like the reported 4,5,6,7-tetrabromobenzotriazole (tbbt), the structurally related 4,5,6,7-tetrabromobenzimidazole (tbbz) was a selective atp-competitive inhibitor of protein kinase ck2 from various sources including yeast, rat liver, neurospora crassa and candida tropicalis, with k(i) values in the range 0.5-1 μm. tbbz was found to virtually inactive vs. pka, pkc, and a very weak inhibitor of protein kinase ck1. tbbt was noted to be a more effective inhibitor of pk60s than of yeast ck2; by contrast, tbbz was a relatively feeble inhibitor of pk60s, thus more selective than tbbt vs. ck2 in yeast cells. therefore, similar to tbbt, tbbz could be regarded as an additional lead compound for development of more potent inhibitors of ck2 [1].
[1] zien, p. ,bretner, m.,zastapilo, k., et al. selectivity of 4,5,6,7-tetrabromobenzimidazole as an atp-competitive potent inhibitor of protein kinase ck2 from various sources. biochemical and biophysical research communications 306(1), 129-133 (2003).
