R. Szyszka et al., HALOGENATED BENZIMIDAZOLES AND BENZOTRIAZOLES AS SELECTIVE INHIBITORSOF PROTEIN-KINASES CK-I AND CK-II FROM SACCHAROMYCES-CEREVISIAE AND OTHER SOURCES, Biochemical and biophysical research communications, 208(1), 1995, pp. 418-424
Several halogeno benzimidazole riboside inhibitors of animal and plant
protein kinases CK I and CK TI (also known as casein kinases I and II
), were found to be effective inhibitors of Saccharomyces cerevisiae C
K IT, but not of the 27-kDa CK I or the 45-kDa CK I. The previously re
ported 5,6-dichloro-2-azabenzimidazole, which preferentially inhibits
plant CK II relative to CK I, discriminates even more effectively betw
een the yeast CK I and CK II enzymes. Two new analogues, tetrahalogeno
-2-azabenzimidazoles, are even more potent inhibitors of CK II and muc
h less so of CK I from yeast and animal sources. Ah inhibitors are com
petitive with respect to ATP (and GTP with CK II), the two latter with
K-i values in the range 0.2 - 0.6 mu M for CK II from yeast and mamma
lian sources. (C) 1995 Academic Press, Inc.