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Chemical Compound Review

Ralenova     1,4-dihydroxy-5,8-bis[2-(2...

Synonyms: Immunex, Novantron, Onkotrone, novatrone, Novantrone, ...
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Disease relevance of Novantron


High impact information on Novantron

  • Lymphokine racketeers? Cistron alleges foul play over IL-1, but Immunex sees it differently [6].
  • Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone [1].
  • PURPOSE: To determine the biologic effect of granulocyte-macrophage colony-stimulating factor (sangramostim, GM-CSF; Immunex Corporation, Seattle, WA) as measured by prostate-specific antigen (PSA) kinetics in patients with serologic progression of prostate cancer after definitive local therapy [7].
  • The release of L1 occurs in mouse and human cells and is blocked by the metalloproteinase inhibitor TAPI (Immunex compound 3) [8].
  • The protease inhibitors, TNFalpha protease inhibitor 1 and Immunex compound 2, could inhibit the production of leptin binding protein, indicating that the enzyme responsible for leptin binding protein cleavage belongs to the metalloprotease family [9].

Chemical compound and disease context of Novantron


Biological context of Novantron


Anatomical context of Novantron

  • In male germ cells, the clinical preparation Novantrone, the dihydrochloride salt of mitoxantrone, did not induce sex-linked recessive lethal mutations in feeding and injection experiments with adult flies, although statistically the results were inconclusive rather than truly negative [19].
  • However, in the present study we observe that 5 mM caffeine reverses the cell kinetic and cytotoxic effects of the intercalating drug Novantrone (mitoxantrone) on L1210, HL-60 and CHO cells [15].
  • The patient was treated with two courses of fludarabine 30 mg/m2 (days 1-5) + Ara-C 2 g/m2 (days 1-5) + novantrone 5 mg/m2 (days 1-3) and G-CSF from day 0 to neutrophil recovery [20].
  • Modified glutathione S-transferase (GST) activity was detected in MCF-7 cell lines selected in vitro for modest levels of resistance (2.6- to 13.7-fold) not only to Adriamycin but also to Novantrone, vincristine (VCR), and etoposide (VP-16) [21].
  • The B cell grows up. B-lymphocyte Development: a UCLA Symposium sponsored by Immunex and Ortho, Park City, UT, USA, March 31-April 6, 1990 [22].

Associations of Novantron with other chemical compounds


Gene context of Novantron

  • The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2) [28].
  • Etanercept (Enbrel, Immunex Corporation, Seattle, Washington, USA) is a new biological disease-modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA) [29].
  • Pretreatment of rats with the immunex monomeric soluble P75 receptor binding protein for TNF-alpha (TNFsr, 0.5 mg/kg, iv) 15 min prior to LPS administration decreased circulating TNF-alpha from 92,137 +/- 12,456 U/ml to undetectable levels as determined by the L929 bioassay [30].
  • The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1 [31].
  • To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT [32].

Analytical, diagnostic and therapeutic context of Novantron


  1. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model. Schally, A.V., Kook, A.I., Monje, E., Redding, T.W., Paz-Bouza, J.I. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  2. Activation of lymphocytes induced by recombinant human granulocyte-macrophage colony-stimulating factor in patients with malignant lymphoma. Ho, A.D., Haas, R., Wulf, G., Knauf, W., Ehrhardt, R., Heilig, B., Körbling, M., Schulz, G., Hunstein, W. Blood (1990) [Pubmed]
  3. Granulocyte-macrophage colony-stimulating factor treatment before doxorubicin and cyclophosphamide chemotherapy priming in women with early-stage breast cancer. Kobrinsky, N.L., Sjolander, D.E., Cheang, M.S., Levitt, R., Steen, P.D. J. Clin. Oncol. (1999) [Pubmed]
  4. Phase I study of recombinant human CD40 ligand in cancer patients. Vonderheide, R.H., Dutcher, J.P., Anderson, J.E., Eckhardt, S.G., Stephans, K.F., Razvillas, B., Garl, S., Butine, M.D., Perry, V.P., Armitage, R.J., Ghalie, R., Caron, D.A., Gribben, J.G. J. Clin. Oncol. (2001) [Pubmed]
  5. Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease. Silver, R.T., Case, D.C., Wheeler, R.H., Miller, T.P., Stein, R.S., Stuart, J.J., Peterson, B.A., Rivkin, S.E., Golomb, H.M., Costanzi, n.u.l.l. J. Clin. Oncol. (1991) [Pubmed]
  6. Lymphokine racketeers? Cistron alleges foul play over IL-1, but Immunex sees it differently. Hopp, T.P. Nat. Biotechnol. (1996) [Pubmed]
  7. Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte-macrophage colony-stimulating factor in patients with serologic progression of prostate cancer. Rini, B.I., Weinberg, V., Bok, R., Small, E.J. J. Clin. Oncol. (2003) [Pubmed]
  8. Metalloproteinase-mediated release of the ectodomain of L1 adhesion molecule. Beer, S., Oleszewski, M., Gutwein, P., Geiger, C., Altevogt, P. J. Cell. Sci. (1999) [Pubmed]
  9. Generation of human soluble leptin receptor by proteolytic cleavage of membrane-anchored receptors. Maamra, M., Bidlingmaier, M., Postel-Vinay, M.C., Wu, Z., Strasburger, C.J., Ross, R.J. Endocrinology (2001) [Pubmed]
  10. MN (N = Novantrone) COP-B therapy on high and intermediate grade non-Hodgkin's lymphoma: an alternative to MA (A = adriamycin) COP-B? Mazza, P., Bocchia, M., Zanchini, R., Gherlinzoni, F., Zinzani, P.L., Pileri, S., Tura, S. Haematologica (1991) [Pubmed]
  11. Prednisone, oral etoposide, and novantrone for treatment of non-Hodgkin's lymphoma: a preliminary report. Goss, P.E., Burkes, R., Rudinskas, L., King, M., Chow, W., Myers, R., Davidson, M., Poldre, P., Crump, M., Sutton, D. Semin. Hematol. (1994) [Pubmed]
  12. Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients. Mauro, F.R., Foa, R., Meloni, G., Gentile, M., Giammartini, E., Giannarelli, D., De Propris, M.S., Rapanotti, M.C., de Fabritiis, P., Mandelli, F. Haematologica (2002) [Pubmed]
  13. Epirubicin versus mitoxantrone in combination chemotherapy for metastatic breast cancer. Pavesi, L., Preti, P., Da Prada, G., Pedrazzoli, P., Poggi, G., Robustelli della Cuna, G. Anticancer Res. (1995) [Pubmed]
  14. Balance between proliferation and apoptosis in leukemic cell lines resistant to cytostatics. Macnamara, B., Palucka, K.A., Porwit-MacDonald, A. Leuk. Lymphoma (1999) [Pubmed]
  15. Caffeine reverses the cytotoxic and cell kinetic effects of Novantrone (mitoxantrone). Traganos, F., Kaminska-Eddy, B., Darzynkiewicz, Z. Cell Prolif. (1991) [Pubmed]
  16. Effects on blood coagulation of adjuvant CNF (cyclophosphamide, novantrone, 5-fluorouracil) chemotherapy in stage II breast cancer patients. Pectasides, D., Tsavdaridis, D., Aggouridaki, C., Tsavdaridou, V., Visvikis, A., Tsatalas, K., Fountzilas, G. Anticancer Res. (1999) [Pubmed]
  17. Knock-in and knock-out. Transgenes, Development and Disease: A Keystone Symposium sponsored by Genentech and Immunex, Tamarron, CO, USA, January 12-18, 1991. Roemer, K., Johnson, P.A., Friedmann, T. New Biol. (1991) [Pubmed]
  18. Role of TWEAK and Fn14 in tumor biology. Winkles, J.A., Tran, N.L., Brown, S.A., Stains, N., Cunliffe, H.E., Berens, M.E. Front. Biosci. (2007) [Pubmed]
  19. The genotoxicity of the anti-cancer drug mitoxantrone in somatic and germ cells of Drosophila melanogaster. Frei, H., Clements, J., Howe, D., Würgler, F.E. Mutat. Res. (1992) [Pubmed]
  20. FLANG (fludarabine + cytosine arabinoside + novantrone + G-CSF) induces partial remission in lymphoid blast transformation of Ph+chronic myelogenous leukaemia. Martinelli, G., Testoni, N., Zuffa, E., Visani, G., Zinzani, P.L., Zaccaria, A., Farabegoli, P., Arpinati, M., Amabile, M., Tura, S. Leuk. Lymphoma (1996) [Pubmed]
  21. Differential increases in glutathione S-transferase activities in a range of multidrug-resistant human tumor cell lines. Whelan, R.D., Hosking, L.K., Townsend, A.J., Cowan, K.H., Hill, B.T. Cancer Commun. (1989) [Pubmed]
  22. The B cell grows up. B-lymphocyte Development: a UCLA Symposium sponsored by Immunex and Ortho, Park City, UT, USA, March 31-April 6, 1990. Manser, T. New Biol. (1990) [Pubmed]
  23. Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome. Rossi, H.A., O'Donnell, J., Sarcinelli, F., Stewart, F.M., Quesenberry, P.J., Becker, P.S. Leukemia (2002) [Pubmed]
  24. Blockade of growth hormone receptor shedding by a metalloprotease inhibitor. Alele, J., Jiang, J., Goldsmith, J.F., Yang, X., Maheshwari, H.G., Black, R.A., Baumann, G., Frank, S.J. Endocrinology (1998) [Pubmed]
  25. Locally advanced breast cancer: defining an optimum treatment regimen. Ahern, V., Barraclough, B., Bosch, C., Langlands, A., Boyages, J. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
  26. Development of a sensitive monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for mitozantrone. Flavell, S.U., Flavell, D.J. J. Immunol. Methods (1988) [Pubmed]
  27. Clinical analysis for the anti-neoplastic agent 1,4-dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino]ethyl)-amino)9,10-anthracenedio ne dihydrochloride (NSC 301739) in plasma. Application of temperature control to provide selectivity in paired-ion high-performance liquid chromatography. Reynolds, D.L., Sternson, L.A., Repta, A.J. J. Chromatogr. (1981) [Pubmed]
  28. Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2. Sha, B.E., Valdez, H., Gelman, R.S., Landay, A.L., Agosti, J., Mitsuyasu, R., Pollard, R.B., Mildvan, D., Namkung, A., Ogata-Arakaki, D.M., Fox, L., Estep, S., Erice, A., Kilgo, P., Walker, R.E., Bancroft, L., Lederman, M.M. AIDS Res. Hum. Retroviruses (2002) [Pubmed]
  29. Etanercept in rheumatoid arthritis. Alldred, A. Expert opinion on pharmacotherapy. (2001) [Pubmed]
  30. In vivo administration of endotoxin and tumor necrosis factor-alpha produce different effects on constitutive and inducible nitric oxide synthase activity in rat neutrophils and aorta ex vivo. Greenberg, S.S., Xie, J., Joseph, K.O., Kolls, J., Summer, W. Proc. Soc. Exp. Biol. Med. (1995) [Pubmed]
  31. Soluble cytokine receptors in biological therapy. Fernandez-Botran, R., Crespo, F.A., Sun, X. Expert opinion on biological therapy. (2002) [Pubmed]
  32. The gallium scan predicts relapse in patients with Hodgkin's disease treated with combined modality therapy. Hagemeister, F.B., Purugganan, R., Podoloff, D.A., Hess, M., Rodriguez, M.A., McLaughlin, P., Swan, F., Romaguera, J.E., Cabanillas, F. Ann. Oncol. (1994) [Pubmed]
  33. Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer. Smith, I.E., Stuart-Harris, R., Pavlidis, N., Bozek, T. Cancer Treat. Rev. (1983) [Pubmed]
  34. Direct determination of mitoxantrone and its mono- and dicarboxylic metabolites in plasma and urine by high-performance liquid chromatography. Payet, B., Arnoux, P., Catalin, J., Cano, J.P. J. Chromatogr. (1988) [Pubmed]
  35. Management of worsening multiple sclerosis with mitoxantrone: a review. Fox, E.J. Clinical therapeutics. (2006) [Pubmed]
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