casein-kinase-ii and Carcinoma--Krebs-2

Several halogeno benzimidazole riboside inhibitors of animal and plant protein kinases CK I and CK II (also known as casein kinases I and II), were found to be effective inhibitors of Saccharomyces cerevisiae CK II, but not of the 27-kDa CK.I or the 45-kDa CK I. The previously reported 5,6-dichloro-2-azabenzimidazole, which preferentially inhibits plant CK II relative to CK I, discriminates even more effectively between the yeast CK I and CK II enzymes. Two new analogues, tetrahalogeno-2-azabenzimidazoles, are even more potent inhibitors of CK II and much less so of CK I from yeast and animal sources. All inhibitors are competitive with respect to ATP (and GTP with CK II), the two latter with Ki values in the range 0.2-0.6 microM for CK II from yeast and mammalian sources.

Topics: Animals; Benzimidazoles; Carcinoma, Krebs 2; Casein Kinase II; Casein Kinases; Kinetics; Liver; Mice; Plants; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Rats; Saccharomyces cerevisiae; Structure-Activity Relationship; Triazoles