ArticleThe Biochemical journal2003
Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA).
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 138 citations in OpenAlex.
- Enhanced inhibitory activity of compounds containing purine scaffolds compared to protein kinase CK2α considering crystalline water.RSC medicinal chemistry · 2024Article
- Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms.Pharmaceutics · 2022Review
- Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study.Molecules (Basel, Switzerland) · 2021Review
- Protein kinase CK2 and ion channels (Review).Biomedical reports · 2020Review
- Discovery of holoenzyme-disrupting chemicals as substrate-selective CK2 inhibitors.Scientific reports · 2019Article
- Novel non-ATP competitive small molecules targeting the CK2 α/β interface.Bioorganic & medicinal chemistry · 2018Article
- Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach.Frontiers in pharmacology · 2018Article
- A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.Bioorganic & medicinal chemistry · 2017Article
- The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Casein Kinase 2 Is Linked to Stress Granule Dynamics through Phosphorylation of the Stress Granule Nucleating Protein G3BP1.Molecular and cellular biology · 2017Article
- Identification of a Potent Allosteric Inhibitor of Human Protein Kinase CK2 by Bacterial Surface Display Library Screening.Pharmaceuticals (Basel, Switzerland) · 2017Article
- Identification of quinones as novel PIM1 kinase inhibitors.Bioorganic & medicinal chemistry letters · 2016Article
- Critical role of Casein kinase 2 in hepatitis C NS5A-mediated inhibition of Kv2.1 K(+) channel function.Neuroscience letters · 2015Article
- An insight into the potentially old-wonder molecule-quercetin: the perspectives in foresee.Chinese journal of integrative medicine · 2015Article
- Article
- Casein kinase II inhibitor enhances production of infectious genotype 1a hepatitis C virus (H77S).PloS one · 2014Article
- Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model.International journal of oncology · 2013Article
- Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines.Journal of hematology & oncology · 2013Article
- A fluorescent reporter of ATP binding-competent receptor kinases.Bioorganic & medicinal chemistry letters · 2012Article
- Structural and functional determinants of protein kinase CK2α: facts and open questions.Molecular and cellular biochemistry · 2011Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IQA [[5-oxo-5,6-dihydro-indolo(1,2-a)quinazolin-7-yl]acetic acid] is a novel ATP/GTP site-directed inhibitor of CK2 ('casein kinase 2'), a pleiotropic and constitutively active protein kinase whose activity is abnormally high in transformed cells. The K (i) value of IQA (0.17 microM) is lower than those of other CK2 inhibitors reported so far. Tested at 10 microM concentration in the presence of 100 microM ATP, IQA almost suppresses CK2 activity in vitro, whereas it is ineffective or weakly effective on a panel of 44 protein kinases and on phosphoinositide 3-kinase. In comparison, other CK2 inhibitors, notably apigenin and quercetin, are more promiscuous. The in vivo efficacy of IQA has been assessed by using the fact that treatment of Jurkat cells with IQA inhibits endogenous CK2 in a dose-dependent manner. IQA has been co-crystallized with maize CK2alpha, which is >70% identical with its human homologue, and the structure of the complex has been determined at 1.68 A (1 A=0.1 nm) resolution. The inhibitor lies in the same plane occupied by the purine moiety of ATP with its more hydrophobic side facing the hinge region. Major contributions to the interaction are provided by hydrophobic forces and non-polar interactions involving the aromatic portion of the inhibitor and the hydrophobic residues surrounding the ATP-binding pocket, with special reference to the side chains of V53 (Val53), I66, M163 and I174. Consequently, mutants of human CK2alpha in which either V66 (the homologue of maize CK2alpha I66) or I174 is replaced by alanine are considerably less sensitive to IQA inhibition when compared with wild-type. These results provide new tools for deciphering the enigmatic role of CK2 in living cells and may pave the way for the development of drugs depending on CK2 activity.
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