title: The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation.
abstract: 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 (CK2α2 β2), consistent with in silico and in vitro analyses.
authors.affiliation: Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cozza
authors.affiliation: Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Venerando
authors.affiliation: Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sarno
authors.affiliation: Department of Biomedical Sciences, University of Padova and CNR Institute of Neurosciences, Via Ugo Bassi 58B, 35131 Padova, Italy.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry* / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D003313:Zea mays / Q000201:enzymology
chemical_list: D000880:Anthraquinones; D047428:Protein Kinase Inhibitors; C543211:1,2,5,8-tetrahydroxy anthraquinone; D047390:Casein Kinase II