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Gene Review

Impdh2  -  inosine 5'-phosphate dehydrogenase 2

Mus musculus

Synonyms: IMP dehydrogenase 2, IMP dehydrogenase type II, IMPD 2, IMPDH 2, IMPDH-II, ...
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Disease relevance of Impdh2


High impact information on Impdh2


Chemical compound and disease context of Impdh2


Biological context of Impdh2


Anatomical context of Impdh2

  • VX-148 does not inhibit proliferation of nonlymphoid cell types such as fibroblasts, indicating selectivity for inhibition of IMPDH activity [13].
  • Chemical modification of the lead compound resulted in pyridazine derivatives with enhanced potency against IMPDH and guanine nucleotide synthesis in cultured cells in vitro and also against guanine nucleotide synthesis in the mouse spleen in vivo [14].
  • The IMP dehydrogenase inhibitors, bredinin and mycophenolic acid (MA), induced, in a dose-dependent manner, the resumption of maturation in cumulus cell-enclosed oocytes maintained in meiotic arrest by hypoxanthine but had no effect on denuded oocytes [15].
  • BACKGROUND: Mycophenolate mofetil (MMF) is a highly potent immunosuppressant that suppresses the proliferation of T and B cells by the uncompetitive inhibition of inosine monophosphate dehydrogenase (IMPDH) [16].
  • Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%) [17].

Associations of Impdh2 with chemical compounds


Other interactions of Impdh2

  • The synthetic material was indistinguishable from biosynthesized TAD as judged by its HPLC behavior, NMR, UV and mass spectra, enzymatic resistance to alkaline phosphatase and susceptibility to venom phosphodiesterase, IMP dehydrogenase inhibitory activity, and cytotoxicity [20].

Analytical, diagnostic and therapeutic context of Impdh2

  • Since inhibitors of IMPDH are in clinical use as immunosuppressive agents, we have examined the consequences of knocking out the IMPDH type II enzyme by gene targeting in a mouse model [6].
  • Purification and sequence analysis confirmed that the abundant protein was IMP dehydrogenase [1].
  • These selections were further refined to discern those likely to have a role in catalysis using information derived from the bacterial and mammalian IMPDH crystal structures and site-specific mutagenesis [21].
  • We used sequence alignments of IMPDH proteins to identify sequence signatures associated with bacterial or eukaryotic IMPDH enzymes [21].
  • Mizoribine (MZ) also inhibits IMPDH in a competitive manner and is used clinically for organ transplantation in Japan as an immunosuppressant with fewer adverse gastrointestinal effects [16].


  1. Increased activity, amount, and altered kinetic properties of IMP dehydrogenase from mycophenolic acid-resistant neuroblastoma cells. Hodges, S.D., Fung, E., McKay, D.J., Renaux, B.S., Snyder, F.F. J. Biol. Chem. (1989) [Pubmed]
  2. Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion. Gu, J.J., Gathy, K., Santiago, L., Chen, E., Huang, M., Graves, L.M., Mitchell, B.S. Blood (2003) [Pubmed]
  3. Studies on the mechanism of action of tiazofurin metabolism to an analog of NAD with potent IMP dehydrogenase-inhibitory activity. Cooney, D.A., Jayaram, H.N., Glazer, R.I., Kelley, J.A., Marquez, V.E., Gebeyehu, G., Van Cott, A.C., Zwelling, L.A., Johns, D.G. Adv. Enzyme Regul. (1983) [Pubmed]
  4. Analysis of the in vitro inhibition of murine and human tumor cell growth by pyrazole derivatives and a substituted azabicyclo [3.1.0] hexane-2,4-dione. Barnes, B.J., Izydore, R.A., Hall, I.H. Anticancer Res. (2001) [Pubmed]
  5. Characterization of mutant murine lymphoma cells with altered inosinate dehydrogenase activities. Ullman, B. J. Biol. Chem. (1983) [Pubmed]
  6. Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene. Gu, J.J., Stegmann, S., Gathy, K., Murray, R., Laliberte, J., Ayscue, L., Mitchell, B.S. J. Clin. Invest. (2000) [Pubmed]
  7. Synergy between imatinib and mycophenolic acid in inducing apoptosis in cell lines expressing Bcr-Abl. Gu, J.J., Santiago, L., Mitchell, B.S. Blood (2005) [Pubmed]
  8. Anti-tumor activity of mycophenolate mofetil against human and mouse tumors in vivo. Tressler, R.J., Garvin, L.J., Slate, D.L. Int. J. Cancer (1994) [Pubmed]
  9. Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin. Barnard, D.L., Day, C.W., Bailey, K., Heiner, M., Montgomery, R., Lauridsen, L., Winslow, S., Hoopes, J., Li, J.K., Lee, J., Carson, D.A., Cottam, H.B., Sidwell, R.W. Antiviral Res. (2006) [Pubmed]
  10. Selective guanosine phosphate deficiency in hepatoma cells induced by inhibitors of IMP dehydrogenase. Kaiser, W.A., Herrmann, B., Keppler, D.O. Hoppe-Seyler's Z. Physiol. Chem. (1980) [Pubmed]
  11. Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and -resistant cell lines. Singh, G., Luna, M.K., Ardalan, B. Cancer Chemother. Pharmacol. (1988) [Pubmed]
  12. Gene amplification and dual point mutations of mouse IMP dehydrogenase associated with cellular resistance to mycophenolic acid. Lightfoot, T., Snyder, F.F. Biochim. Biophys. Acta (1994) [Pubmed]
  13. Characterization of pharmacological efficacy of VX-148, a new, potent immunosuppressive inosine 5'-monophosphate dehydrogenase inhibitor. Jain, J., Almquist, S.J., Heiser, A.D., Shlyakhter, D., Leon, E., Memmott, C., Moody, C.S., Nimmesgern, E., Decker, C. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  14. A novel series of non-nucleoside inhibitors of inosine 5'-monophosphate dehydrogenase with immunosuppressive activity. Franklin, T.J., Morris, W.P., Jacobs, V.N., Culbert, E.J., Heys, C.A., Ward, W.H., Cook, P.N., Jung, F., Plé, P. Biochem. Pharmacol. (1999) [Pubmed]
  15. Maintenance of murine oocyte meiotic arrest: uptake and metabolism of hypoxanthine and adenosine by cumulus cell-enclosed and denuded oocytes. Downs, S.M., Coleman, D.L., Eppig, J.J. Dev. Biol. (1986) [Pubmed]
  16. Combination effect of mycophenolate mofetil with mizoribine on cell proliferation assays and in a mouse heart transplantation model. Shimmura, H., Tanabe, K., Habiro, K., Abe, R., Toma, H. Transplantation (2006) [Pubmed]
  17. Synthesis, structure, and antiproliferative activity of selenophenfurin, an inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin. Franchetti, P., Cappellacci, L., Sheikha, G.A., Jayaram, H.N., Gurudutt, V.V., Sint, T., Schneider, B.P., Jones, W.D., Goldstein, B.M., Perra, G., De Montis, A., Loi, A.G., La Colla, P., Grifantini, M. J. Med. Chem. (1997) [Pubmed]
  18. New antitumor imidazole derivative, 5-carbamoyl-1H-imidazol-4-yl piperonylate, as an inhibitor of purine synthesis and its activation by adenine phosphoribosyltransferase. Fukui, M., Inaba, M., Tsukagoshi, S., Sakurai, Y. Cancer Res. (1982) [Pubmed]
  19. Studies on the mechanism of action of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide). VI. Biochemical and pharmacological studies on the degradation of thiazole-4-carboxamide adenine dinucleotide (TAD). Ahluwalia, G.S., Cooney, D.A., Marquez, V.E., Jayaram, H.N., Johns, D.G. Biochem. Pharmacol. (1986) [Pubmed]
  20. Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase. Gebeyehu, G., Marquez, V.E., Kelley, J.A., Cooney, D.A., Jayaram, H.N., Johns, D.G. J. Med. Chem. (1983) [Pubmed]
  21. Differential signatures of bacterial and mammalian IMP dehydrogenase enzymes. Zhang, R., Evans, G., Rotella, F., Westbrook, E., Huberman, E., Joachimiak, A., Collart, F.R. Current medicinal chemistry. (1999) [Pubmed]
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