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Characterization of human type I and type II IMP dehydrogenases.
Human IMP dehydrogenase, a target for anticancer and immunosuppressive chemotherapy, exists as two isoforms, types I and II, which have identical inhibition patterns and inhibition constants. Expand
Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias.
Observations suggest that expression of type II IMPDH is stringently linked with immature characteristics of leukemic cells; thus, it should be a selective target for antileukemic chemotherapy. Expand
Two distinct cDNAs for human IMP dehydrogenase.
This is the first report suggesting the existence of two distinct types of human IMP dehydrogenase molecular species which may have different sensitivities to the drugs targeted against IMP dehydrogensase. Expand
Proliferation-linked regulation of type II IMP dehydrogenase gene in human normal lymphocytes and HL-60 leukemic cells.
The low level of type II IMPDH mRNA in normal lymphocytes was up-regulated by phytohemagglutinin stimulation, and the type II mRNA expression in quiescent HL-60 cells was also elevated 2.8-fold by serum stimulation. Expand
Regulation of GTP biosynthesis.
In support of enzyme-pattern-targeted chemotherapy, evidence was provided for synergistic chemotherapy with tiazofurin (inhibitor of IMPDH) and hypoxanthine (competitive inhibitor of GPRT and guanine salvage activity) in patients and in tissue culture cell lines. Expand
Biochemically directed therapy of leukemia with tiazofurin, a selective blocker of inosine 5'-phosphate dehydrogenase activity.
Tiazofurin was better tolerated in most patients than other antileukemic treatment modalities and provided a rational,Biochemically targeted, and biochemically monitored chemotherapy which should be of interest in the treatment of leukemias and as a paradigm in enzyme pattern-targeted chemotherapy. Expand
Action of the active metabolites of tiazofurin and ribavirin on purified IMP dehydrogenase.
The results provide a biochemical basis for combination chemotherapy with tiazofurin and ribavirin targeted against the two different ligand sites of IMP dehydrogenase, with higher affinities than the natural substrates and products. Expand
Mycophenolic acid, an inhibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells.
It is suggested that inducible NO synthase activity is dependent on GTP level and can be blocked by curtailing IMP dehydrogenase activity. Expand
Human Type I and II IMP Dehydrogenases as Drug Targets
  • Y. Natsumeda, S. Carr
  • Biology, Medicine
  • Annals of the New York Academy of Sciences
  • 1 November 1993
Tissue-differential expression of two distinct genes for human IMP dehydrogenase (E.C.
It is demonstrated that both type I and type II IMPDH genes are widely distributed among various species by Southern blot analysis and Interestingly, type I IM PDH gene may have multiple gene families in primates. Expand