Casein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole of specific RNA polymerase II transcription.

Zandomeni, Rubén; Zandomeni, M C; Shugar, David; Weinmann, Roberto

doi:10.1016/s0021-9258(17)35799-x

Cited by 272 publications

(27 citation statements)

References 23 publications

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“…Not surprisingly, therefore, an increasing number of recent reports deal with pharmacological inhibition of CK2 by a variety of compounds. These include flavonoids, notably apigenin [23] (whose selectivity, however, is quite modest [24]), emodin [25], and other condensed polyphenolic compounds [26], the indoloquinazolin derivative IQA [24,27], and a variety of halogenated benzimidazole/triazole compounds developed from the original molecule DRB [28,29]. The one most successfully used at present is 4,5,6,7-tetrabromo-1-benzotriazole (TBB), a very selective, cell-permeable CK2 inhibitor [30] that is proving useful in documenting the implication of CK2 in a variety of cell functions (notably apoptosis [31], repair of chromosomal DNA single-strand breaks [32], functionality of the pleiotropic cochaperone CDC-37 [33], and upregulation of the Akt signaling pathway [34]) and in identifying new protein targets of CK2 (reviewed in [35]).…”

Section: Introductionmentioning

confidence: 99%

Inspecting the Structure-Activity Relationship of Protein Kinase CK2 Inhibitors Derived from Tetrabromo-Benzimidazole

Battistutta

Mazzorana

Sarno

et al. 2005

Chemistry & Biology

114

118

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CK2 is a very pleiotropic protein kinase whose high constitutive activity is suspected to cooperate to neoplasia. Here, the crystal structure of the complexes between CK2 and three selective tetrabromo-benzimidazole derivatives inhibiting CK2 with Ki values between 40 and 400 nM are presented. The ligands bind to the CK2 active site in a different way with respect to the parent compound TBB. They enter more deeply into the cavity, establishing halogen bonds with the backbone of Glu114 and Val116 in the hinge region. A detailed analysis of the interactions highlights a major role of the hydrophobic effect in establishing the rank of potency within this class of inhibitors and shows that polar interactions are responsible for the different orientation of the molecules in the active site.

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Section: Introductionmentioning

confidence: 99%

Inspecting the Structure-Activity Relationship of Protein Kinase CK2 Inhibitors Derived from Tetrabromo-Benzimidazole

Battistutta

Mazzorana

Sarno

et al. 2005

Chemistry & Biology

114

118

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“…The experimental design of the electrophysi-580 J Soc Gynecol Investig Vol. 13 25,000g for 15 minutes. Since the amount of NMM-1I-B remaining in the pellets was minimal (<5%-, not shown), the pellets were discarded.…”

Section: Cell Culturesmentioning

confidence: 99%

Non-Muscle Myosin-II-B Filament Regulation of Paracellular Resistance in Cervical Epithelial Cells Is Associated With Modulation of the Cortical Acto-Myosin

Gorodeski

2006

Journal of the Society for Gynecologic Investigation

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Objective-To understand myosin regulation of epithelial permeability.Methods-Experimental study, using human cervical epithelial cells CaSki. Endpoints were paracellular permeability (determined in terms of transepithelial electrical resistance); non-muscle myosin-II-B (NMM-II-B) cellular localization; NMM-II-B phosphorylation status; NMM-II-Bactin interaction (determined in-vitro by the immunoprecipitation-immunoreactivity method); and NMM-II-B filamentation (determined in-vitro using purified NMM-II-B filaments in terms of filaments disassembly / assembly ratios. Results- Conclusions-The results suggest that NMM-II-B filaments are in steady-state equilibrium of phosphorylation-dephosphorylation mediated by CK2 and by ROCK-regulated myosin heavy chain phosphatase, respectively. Increased phosphorylation would tend to inhibit assembly of NMM-II-B filaments and lead to decreased actin-myosin interaction, which would tend to decrease the R LIS and increase the paracellular permeability.

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“…Among them, ATP-competitive inhibitors, halogenated benzotriazole, and benzimidazole derivatives play an important role. Following 5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (DRB) [ 13 ], 4,5,6,7-tetrabromo-1 H -benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1 H -benzimidazole (TBBz) were identified as strong and selective kinase CK2 inhibitors [ 14 ]. Further studies on these compounds resulted in the synthesis of numerous potent kinase CK2 inhibitors, including 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (DMAT) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…1 H-NMR (500 MHz, d-DMSO) δ 7.02-7.10 (2H, m, ArH), 7.10-7.16 (2H, m, ArH),11.90 (2H, s, 2xOH);13 C-NMR (125 MHz, d-DMSO) δ 115.12, 123.00, 125.60, 155.17; HRMS calcd. for C 8 H 7 N 2 O 2 [M + H] + : 163.05020, found: 163.05011.…”

mentioning

confidence: 99%

Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2

et al. 2021

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Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability, apoptosis, cell proliferation and survival, angiogenesis, or ER-stress response. As CK2 activity is found perturbed in many pathological states, including cancers, it becomes an attractive target for the pharma. A large number of low-mass ATP-competitive inhibitors have already been developed, the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic ligands derived from the commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand series were selected to enable the separation of the scaffold effect from the hydrophobic interactions attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied to test the capability of each ligand for binding at the ATP-binding site of CK2. HPLC-derived ligand hydrophobicity data are compared with the binding affinity assessed by low-volume differential scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory activity against CK2α and toxicity against four reference cell lines have been determined for eight compounds identified as the most promising in nanoDSF assay.

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Casein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole of specific RNA polymerase II transcription.

Cited by 272 publications

References 23 publications

Inspecting the Structure-Activity Relationship of Protein Kinase CK2 Inhibitors Derived from Tetrabromo-Benzimidazole

Inspecting the Structure-Activity Relationship of Protein Kinase CK2 Inhibitors Derived from Tetrabromo-Benzimidazole

Non-Muscle Myosin-II-B Filament Regulation of Paracellular Resistance in Cervical Epithelial Cells Is Associated With Modulation of the Cortical Acto-Myosin

Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2

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