Halogenated benzimidazoles and benzotriazoles as selective inhibitors of protein kinases CK I and CK II from Saccharomyces cerevisiae and other sources

Biochem Biophys Res Commun. 1995 Mar 8;208(1):418-24. doi: 10.1006/bbrc.1995.1354.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Carcinoma, Krebs 2 / enzymology*
  • Casein Kinase II
  • Casein Kinases
  • Kinetics
  • Liver / enzymology*
  • Mice
  • Plants / enzymology
  • Protein Kinase Inhibitors*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Rats
  • Saccharomyces cerevisiae / enzymology*
  • Structure-Activity Relationship
  • Triazoles / pharmacology*

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Triazoles
  • Casein Kinase II
  • Casein Kinases
  • Protein Serine-Threonine Kinases