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Usage

Uses

Used in Pharmaceutical Industry:
TBBZ is used as a CK2 inhibitor for its potential role in the development of novel therapeutic strategies against various diseases. Its selective inhibition of CK2 makes it a valuable tool in understanding the role of this enzyme in cellular processes and its potential as a target for drug development.
Used in Research Applications:
TBBZ is used as a CK2 inhibitor in HeLa cells and rat septal neurons, allowing researchers to study the effects of CK2 inhibition on cellular processes and the potential implications for disease treatment.
Used in Biochemical Studies:
TBBZ's selective inhibition of CK2 makes it a useful tool in biochemical studies, where it can be employed to investigate the role of CK2 in various cellular pathways and its potential as a therapeutic target.
Used in Drug Development:
TBBZ's properties as a CK2 inhibitor make it a promising candidate for the development of new drugs targeting CK2-related diseases. Its selective inhibition of CK2 can be leveraged to design more effective and targeted therapies with fewer side effects.

Biological Activity

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.

Biochem/physiol Actions

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.

in vitro

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].

references

[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).

Upstream product

• 51-17-2 benzoimidazole 

Relevant academic research and scientific papers

A subnanomolar fluorescent probe for protein kinase CK2 interaction studies

Up-regulation of an acidophilic protein kinase, CK2, has been established in several types of cancer. This cognition has made CK2 an important target for drug development for cancer chemotherapy. The characterization of potential drug candidates, determination of the structure and clarification of the functions of CK2 could be facilitated by the application of small-molecule fluorescent probes that bind to the active site of the enzyme with high affinity and selectivity. We have used a bisubstrate approach for the development of a highly potent inhibitor of CK2. 4,5,6,7-Tetrabromo-1H-benzimidazole was conjugated with peptides containing multiple aspartate residues via different linkers. The design of the inhibitors was by crystallographic analysis of the complex of an inhibitor with the catalytic subunit of the enzyme (CK2α). The inhibitory potency of the synthesized compounds was established in a kinetic assay that used thin layer chromatography for the measurement of the rate of phosphorylation of fluorescently labelled peptide 5-TAMRA-RADDSDDDDD. The most potent inhibitor, ARC-1502 (Ki = 0.5 nM), revealed high selectivity for CK2α in a panel of 140 protein kinases. Labelling of ARC-1502 with PromoFluor-647 gave the fluorescent probe ARC-1504 that possessed subnanomolar affinity towards both CK2α and the holoenzyme. The probe was used in a fluorescence anisotropy-based binding assay to measure the concentration of CK2α and characterize non-labelled ligands binding to the active site of CK2α.

Synthesis of novel proxyphylline derivatives with dual Anti-Candida albicans and anticancer activity

Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R ≥ 3 at conc. of 31, 36 and 20 μM, respectively) however not against normal mammalian Vero cell line in vitro (IC50 ≥ 280 μM) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 μM) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3–6.5 μM). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections.

Synthesis and activity of 1H-benzimidazole and 1H-benzotriazole derivatives as inhibitors of Acanthamoeba castellanii

Chloro-, bromo- and methyl- analogues of 1H-benzimidazole and 1H-benzotriazole and their N-alkyl derivatives have been synthesized and tested in vitro against the protozoa Acanthamoeba castellanii. The results indicate that 5,6-dimethyl-1H-benzotriazole (11) and 5,6-dibromo-1H-benzotriazole (14) have higher efficacy than the antiprotozoal agent chlorohexidine.