The selectivity of inhibitors of protein kinase CK2: an update

• DOI: 10.1042/bj20080309
• Publication Date: 2008-07-02T12:37:27Z
• Authors: Mario A. Pagano; Jenny Bain; Zygmunt Kazimierczuk; Stefania Sarno; Maria Ruzzene; Giovanni Di Maira; Matthew Elliott; Andrzej Orzeszko; Giorgio Cozza; Flavio Meggio; Lorenzo A. Pinna
• Keywords: Casein kinase 2; DYRK1A; Benzimidazole; PIM1

CK2 (casein kinase 2) is a very pleiotropic serine/threonine protein whose abnormally high constitutive activity has often been correlated to pathological conditions with special reference neoplasia. The two most widely used cell permeable inhibitors, TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole), are marketed as quite specific blockers. In the present study we show, by using panel of approx. 80 kinases, that its parent compound TBI (or TBBz; 4,5,6,7-tetrabromo-1H-benzimidazole) potent inhibitors several other PIM (provirus integration site for Moloney murine leukaemia virus)1, PIM2, PIM3, PKD1 (protein D1), HIPK2 (homeodomain-interacting DYRK1a (dual-specificity tyrosine-phosphorylated -regulated 1a). contrast, significantly more selective toward CK2, although it also inhibits PIM1 PIM3. an attempt improve selectivity towards library 68 TBB/TBI-related compounds have tested their ability discriminate between PIM1, DYRK1a, ending up seven efficacy markedly higher than second inhibited kinase. Two these, K64 (3,4,5,6,7-pentabromo-1H-indazole) K66 (1-carboxymethyl-2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole), display overall much when on kinases similar inducers apoptosis.