The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation
Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Am...
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doaj-3048e182ebc5419abe8850586a30b0d12020-11-25T00:18:38ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/734127734127The Selectivity of CK2 Inhibitor Quinalizarin: A ReevaluationGiorgio Cozza0Andrea Venerando1Stefania Sarno2Lorenzo A. Pinna3Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, ItalyMany polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) turned out to be particularly potent (Ki = 0.058 μM) and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX-4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2α) and CK2 holoenzyme (CK2α2β2), consistent with in silico and in vitro analyses.http://dx.doi.org/10.1155/2015/734127 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giorgio Cozza Andrea Venerando Stefania Sarno Lorenzo A. Pinna |
spellingShingle |
Giorgio Cozza Andrea Venerando Stefania Sarno Lorenzo A. Pinna The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation BioMed Research International |
author_facet |
Giorgio Cozza Andrea Venerando Stefania Sarno Lorenzo A. Pinna |
author_sort |
Giorgio Cozza |
title |
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation |
title_short |
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation |
title_full |
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation |
title_fullStr |
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation |
title_full_unstemmed |
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation |
title_sort |
selectivity of ck2 inhibitor quinalizarin: a reevaluation |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) turned out to be particularly potent (Ki = 0.058 μM) and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX-4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2α) and CK2 holoenzyme (CK2α2β2), consistent with in silico and in vitro analyses. |
url |
http://dx.doi.org/10.1155/2015/734127 |
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