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Chemical Compound Review

AC1NSI8H     2-[[(1Z)-1- (diaminomethylidenehydrazinyli d...

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Disease relevance of MITOGUAZONE


High impact information on MITOGUAZONE


Chemical compound and disease context of MITOGUAZONE


Biological context of MITOGUAZONE

  • In contrast, the incorporation of [methyl-3H]thymidine into DNA and the rate of entry of the cells into mitosis are inhibited by 60% in the presence of MGBG [14].
  • A haploid yeast strain was transformed with a genomic minitransposon- and lacZ-tagged library, and positive clones were selected for growth resistance to methylglyoxal bis(guanylhydrazone) (MGBG), a toxic polyamine analog [15].
  • A 747-bp DNA fragment adjacent to the lacZ fusion gene rescued from one MGBG-resistant clone mapped to chromosome X within the coding region of a putative Ser/Thr protein kinase gene of previously unknown function (YJR059w, or STK2) [15].
  • Exposure of cultured leukemia L1210 cells to 0.1 micron methylglyoxal-bis(guanylhydrazone) resulted in a concentration-dependent inhibition of cellular proliferation, beginning after about 1 to 2 generation times (12 to 24 hr) [16].
  • Against L1210 leukemic cells and T24 bladder carcinoma cells, the compounds were slightly less effective than MGBG at inhibiting cell growth, with 50% inhibitory concentration values of 1 to 10 microM as compared with 0.5 and 1.1 microM, respectively, for MGBG [17].

Anatomical context of MITOGUAZONE

  • In both cell lines, polyamines and MGBG share a common transport system [18].
  • After removal of MGBG, damaged mitochondria in 90 to 95% of cells recovered near-normal ultrastructure within 1 to 2 days; in some cells, mitochondrial recovery from severe damage could be monitored following a lag period of up to 5 days [19].
  • Moreover, current results indicate that MGBG has useful antitumor activity in patients with advanced malignant lymphoma and carcinomas of the head and neck, esophagus, and lung (non-small cell) [20].
  • DBI was found to increase markedly the inhibitory effect of either 4,4'-diacetyldiphenylurea-bis(guanylhydrazone) or MGBG on respiration of isolated rat liver mitochondria [21].
  • Polyamines and biosynthetic enzymes in the rat intestinal mucosa and the influence of methylglyoxal-bis(guanylhydrazone) [2].

Associations of MITOGUAZONE with other chemical compounds

  • The Km and Vmax values for spermidine and MGBG measured 10 sec after addition (initial permeation) were not affected by DFMO pretreatment in either cell line [18].
  • Ethylglyoxal bis(guanylhydrazone) (EGBG) was compared as an inhibitor of polyamine biosynthesis with methylglyoxal bis(guanylhydrazone) (MGBG) in bovine small lymphocytes stimulated by concanavalin A [22].
  • Proliferation of 9L cells was only slightly inhibited by treatment with 40 microM MGBG alone, but when used in combination with 0.5 mM alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, proliferation was much more effectively inhibited [18].
  • In contrast to MGBG, CGP 48664 displays attenuated antimitochondrial activity as indicated by a lack of effect on pyruvate oxidation and mitochondrial DNA levels under treatment conditions which inhibit cell proliferation [23].
  • As with MGBG and 4,4'-diacetyldiphenylurea-bis(guanylhydrazone), the potassium cationophore, valinomycin, increased the sensitivity of mitochondrial respiration to DBI [21].

Gene context of MITOGUAZONE


Analytical, diagnostic and therapeutic context of MITOGUAZONE


  1. Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma. Warrell, R.P., Lee, B.J., Kempin, S.J., Lacher, M.J., Straus, D.J., Young, C.W. Blood (1981) [Pubmed]
  2. Polyamines and biosynthetic enzymes in the rat intestinal mucosa and the influence of methylglyoxal-bis(guanylhydrazone). Porter, C.W., Dworaczyk, D., Ganis, B., Weiser, M.M. Cancer Res. (1980) [Pubmed]
  3. Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate. Scher, H.I., Yagoda, A., Ahmed, T., Watson, R.C. J. Clin. Oncol. (1985) [Pubmed]
  4. A selective effect of methylglyoxal-bis(guanylhydrazone) on the synthesis of mitochondrial DNA of cultured L1210 leukemia cells. Feuerstein, B., Porter, C.W., Dave, C. Cancer Res. (1979) [Pubmed]
  5. Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. Zhang, M., Caragine, T., Wang, H., Cohen, P.S., Botchkina, G., Soda, K., Bianchi, M., Ulrich, P., Cerami, A., Sherry, B., Tracey, K.J. J. Exp. Med. (1997) [Pubmed]
  6. Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone. Bianchi, M., Bloom, O., Raabe, T., Cohen, P.S., Chesney, J., Sherry, B., Schmidtmayerova, H., Calandra, T., Zhang, X., Bukrinsky, M., Ulrich, P., Cerami, A., Tracey, K.J. J. Exp. Med. (1996) [Pubmed]
  7. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Hommes, D., van den Blink, B., Plasse, T., Bartelsman, J., Xu, C., Macpherson, B., Tytgat, G., Peppelenbosch, M., Van Deventer, S. Gastroenterology (2002) [Pubmed]
  8. Fetuin (alpha2-HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules. Wang, H., Zhang, M., Bianchi, M., Sherry, B., Sama, A., Tracey, K.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus. Forastiere, A.A., Gennis, M., Orringer, M.B., Agha, F.P. J. Clin. Oncol. (1987) [Pubmed]
  10. MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease. Hagemeister, F.B., Tannir, N., McLaughlin, P., Salvador, P., Riggs, S., Velasquez, W.S., Cabanillas, F. J. Clin. Oncol. (1987) [Pubmed]
  11. TATA-binding protein-associated factor 7 regulates polyamine transport activity and polyamine analog-induced apoptosis. Fukuchi, J., Hiipakka, R.A., Kokontis, J.M., Nishimura, K., Igarashi, K., Liao, S. J. Biol. Chem. (2004) [Pubmed]
  12. Synergistic antileukemic effect of two polyamine synthesis inhibitors. Host survival and cell-cycle kinetic analysis. Ask, A., Persson, L., Oredsson, S.M., Heby, O. Int. J. Cancer (1986) [Pubmed]
  13. Methyl-glyoxal bis guanyl hydrazone (methyl-GAG, MGBG) in advanced breast cancer. A Phase II trial of the Southwest Oncology Group. Knight, W.A., O'Bryan, R.M., Samal, B., Costanzi, J.J. Investigational new drugs. (1984) [Pubmed]
  14. Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A. Fillingame, R.H., Jorstad, C.M., Morris, D.R. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  15. The STK2 gene, which encodes a putative Ser/Thr protein kinase, is required for high-affinity spermidine transport in Saccharomyces cerevisiae. Kaouass, M., Audette, M., Ramotar, D., Verma, S., De Montigny, D., Gamache, I., Torossian, K., Poulin, R. Mol. Cell. Biol. (1997) [Pubmed]
  16. Morphological evidence for an antimitochondrial action by methylglyoxal-bis(guanylhydrazone). Pathak, S.N., Porter, C.W., Dave, C. Cancer Res. (1977) [Pubmed]
  17. New S-adenosylmethionine decarboxylase inhibitors with potent antitumor activity. Regenass, U., Caravatti, G., Mett, H., Stanek, J., Schneider, P., Müller, M., Matter, A., Vertino, P., Porter, C.W. Cancer Res. (1992) [Pubmed]
  18. Modification of uptake and antiproliferative effect of methylglyoxal bis(guanylhydrazone) by treatment with alpha-difluoromethylornithine in rodent cell lines with different sensitivities to methylglyoxal bis(guanylhydrazone). Alhonen-Hongisto, L., Levin, V.A., Marton, L.J. Cancer Res. (1985) [Pubmed]
  19. Analysis of methylglyoxal bis(guanylhydrazone)-induced alterations of hamster tumor mitochondria by correlated studies of selective rhodamine binding, ultrastructural damage, DNA replication, and reversibility. Nass, M.M. Cancer Res. (1984) [Pubmed]
  20. Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects. Warrell, R.P., Burchenal, J.H. J. Clin. Oncol. (1983) [Pubmed]
  21. Potentiation of the antimitochondrial and antiproliferative effects of bis(guanylhydrazones) by phenethylbiguanide. Byczkowski, J.Z., Zychlinski, L., Porter, C.W. Cancer Res. (1982) [Pubmed]
  22. Comparison of specificity of inhibition of polyamine synthesis in bovine lymphocytes by ethylglyoxal bis(guanylhydrazone) and methylglyoxal bis(guanylhydrazone). Igarashi, K., Porter, C.W., Morris, D.R. Cancer Res. (1984) [Pubmed]
  23. CGP 48664, a new S-adenosylmethionine decarboxylase inhibitor with broad spectrum antiproliferative and antitumor activity. Regenass, U., Mett, H., Stanek, J., Mueller, M., Kramer, D., Porter, C.W. Cancer Res. (1994) [Pubmed]
  24. The tetravalent guanylhydrazone CNI-1493 blocks the toxic effects of interleukin-2 without diminishing antitumor efficacy. Kemeny, M.M., Botchkina, G.I., Ochani, M., Bianchi, M., Urmacher, C., Tracey, K.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  25. Inhibitors of polyamine biosynthesis affect the expression of genes encoding cytoskeletal proteins. Kamińska, B., Kaczmarek, L., Grzelakowska-Sztabert, B. FEBS Lett. (1992) [Pubmed]
  26. Induction of ornithine decarboxylase activity in mouse tissues by phorbol ester is effectively blocked by methylglyoxal bis(butylamidinohydrazone). Hibasami, H., Tsukada, T., Maekawa, S., Sakurai, M., Nakashima, K. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  27. Localization of S-adenosylmethionine decarboxylase in murine tissues by immunohistochemistry. Gritli-Linde, A., Holm, I., Linde, A. Eur. J. Oral Sci. (1995) [Pubmed]
  28. Penetration of methylglyoxal bis(guanylhydrazone) into intracerebral tumors in humans. Rosenblum, M.G., Stewart, D.J., Yap, B.S., Leavens, M., Benjamin, R.S., Loo, T.L. Cancer Res. (1981) [Pubmed]
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