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 M) 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 (CK2) and CK2 holoenzyme (CK2 2 β 2), consistent with in silico and in vitro analyses.