2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole: a novel powerful and selective inhibitor of protein kinase CK2.
Protein kinase CK2 is a highly pleiotropic enzyme whose high constitutive activity is suspected to be instrumental to the enhancement of the tumour phenotype and to the propagation of infectious diseases. Here we describe a novel compound, 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), which is superior to the commonly used specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in several respects. DMAT displays the lowest K(i) value ever reported for a CK2 inhibitor (40 nM); it is cell permeable and its efficacy on cultured cells, both in terms of endogenous CK2 inhibition and induction of apoptosis, is several fold higher than that of TBB. The selectivity of DMAT assayed on a panel of >30 protein kinases is comparable to that of TBB, with the additional advantage of being ineffective on protein kinase CK1 up to 200 microM. These properties make DMAT the first choice CK2 inhibitor for in vivo studies available to date.
Pagano
Mario A
MA
Dipartimento di Chimica Biologica, Università di Padova, Italy.
Meggio
Flavio
F
Ruzzene
Maria
M
Andrzejewska
Mariola
M
Kazimierczuk
Zygmunt
Z
Pinna
Lorenzo A
LA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D047390:Casein Kinase II; D047388:Casein Kinases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D007700:Kinetics; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D014230:Triazoles / Q000494:pharmacology
C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; C405354:4,5,6,7-tetrabromobenzotriazole; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D014230:Triazoles; D047390:Casein Kinase II; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases