Biochem. Biophys. Res. Commun. 2004, 321, 1040-1044.
Pagano, M.A., Meggio, F., Ruzzene, M.,
Andrzejewska, M., Kazimierczuk, Z. and
Pinna, L.A. (2004):
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
Ki value ever reported for a CK2 inhibitor (40nM); 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
mM. These
properties make DMAT the first choice CK2 inhibitor for in vivo studies
available to date.
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