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.

The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation / Cozza, Giorgio; Venerando, Andrea; Sarno, Stefania; Pinna, Lorenzo A.. - In: BIOMED RESEARCH INTERNATIONAL. - ISSN 2314-6133. - 2015(2015). [10.1155/2015/734127]

The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation

VENERANDO, ANDREA;
2015

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.
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation / Cozza, Giorgio; Venerando, Andrea; Sarno, Stefania; Pinna, Lorenzo A.. - In: BIOMED RESEARCH INTERNATIONAL. - ISSN 2314-6133. - 2015(2015). [10.1155/2015/734127]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2915995
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 22
social impact