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Chemical Compound Review

Ornidyl     2,5-diamino-2- (difluoromethyl)pentanoic acid

Synonyms: Eflornitina, EFLORNITHINE, dfmo, Eflornithinum, RMI 71782, ...
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Disease relevance of Ornidyl


Psychiatry related information on Ornidyl

  • RESULTS: Predictable shifts in auditory thresholds occurred following administration of eflornithine [5].
  • While having no influence per se on pain threshold, DFMO significantly inhibited the analgesic activity of morphine (15 mg/kg i.p.), this effect being obtained when brain ODC activity was reduced by at least 80% [6].
  • Use of a self-assessment questionnaire to assess the effect of study treatment on 6 aspects of patient well-being showed that eflornithine reduced the mean level of overall discomfort and bother by 33 versus 15% in placebo recipients [7].

High impact information on Ornidyl

  • There appear to be both ODC-dependent and ODC-independent processes contributing to the subcellular mechanisms associated with growth, which must be considered in the potential laboratory and clinical use of DFMO [1].
  • Mechanisms of antitrypanosomal action of these drugs are mostly unknown, except for eflornithine, which is a suicide inhibitor of ornithine decarboxylase [8].
  • METHODS: Noncancerous, preimmortal breast epithelial cells derived from a patient with LFS were treated for 3 months with nontoxic concentrations of the chemopreventive agents oltipraz, difluoromethylornithine, tamoxifen, and retinoic acid or with two different telomerase inhibitors [9].
  • BACKGROUND: Oral eflornithine in combination with intravenous mitoguazone (methylbisguanylhydrazone) has shown activity against recurrent anaplastic gliomas [2].
  • PURPOSE: This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas [2].

Chemical compound and disease context of Ornidyl


Biological context of Ornidyl


Anatomical context of Ornidyl


Associations of Ornidyl with other chemical compounds


Gene context of Ornidyl

  • Western blot analysis revealed that treatment of RASMC with NO or DFMO leads to activation of p42/p44 MAPK and induction of p21(waf1/cip1) [29].
  • Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein [11].
  • We found that DFMO caused a p53-independent increase in p21 and its association with cyclin-dependent kinase (cdk)-2 and decreased cdk-2 protein as well as its phosphorylation on Thr160 [11].
  • MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression [11].
  • When K14-MEK mice were given alpha-difluoromethylornithine (DFMO), a suicide inactivator of ODC, in the drinking water from birth, there was a dramatic delay in the onset of tumor growth ( approximately 6 weeks), and only 25% of DFMO-treated mice developed tumors by 15 weeks of age [30].

Analytical, diagnostic and therapeutic context of Ornidyl


  1. Role of ornithine decarboxylase in cardiac growth and hypertrophy. Bartolome, J., Huguenard, J., Slotkin, T.A. Science (1980) [Pubmed]
  2. Treatment of recurrent gliomas with eflornithine. Levin, V.A., Prados, M.D., Yung, W.K., Gleason, M.J., Ictech, S., Malec, M. J. Natl. Cancer Inst. (1992) [Pubmed]
  3. Difluoromethylornithine for arseno-resistant Trypanosoma brucei gambiense sleeping sickness. Pepin, J., Milord, F., Guern, C., Schechter, P.J. Lancet (1987) [Pubmed]
  4. Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness. Milord, F., Pépin, J., Loko, L., Ethier, L., Mpia, B. Lancet (1992) [Pubmed]
  5. alpha-difluoromethylornithine ototoxicity. Chemoprevention clinical trial results. Pasic, T.R., Heisey, D., Love, R.R. Arch. Otolaryngol. Head Neck Surg. (1997) [Pubmed]
  6. ODC-polyamine system is involved in morphine analgesia. Genedani, S., Bernardi, M., Tagliavini, S., Bertolini, A. Life Sci. (1989) [Pubmed]
  7. Topical eflornithine. Balfour, J.A., McClellan, K. American journal of clinical dermatology. (2001) [Pubmed]
  8. Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis. Wang, C.C. Annu. Rev. Pharmacol. Toxicol. (1995) [Pubmed]
  9. Effects of chemopreventive and antitelomerase agents on the spontaneous immortalization of breast epithelial cells. Herbert, B.S., Wright, A.C., Passons, C.M., Wright, W.E., Ali, I.U., Kopelovich, L., Shay, J.W. J. Natl. Cancer Inst. (2001) [Pubmed]
  10. Efficacy of combinations of difluoromethylornithine and bleomycin in a mouse model of central nervous system African trypanosomiasis. Clarkson, A.B., Bacchi, C.J., Mellow, G.H., Nathan, H.C., McCann, P.P., Sjoerdsma, A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  11. Interaction between Polyamines and the Mitogen-Activated Protein Kinase Pathway in the Regulation of Cell Cycle Variables in Breast Cancer Cells. Hu, X., Washington, S., Verderame, M.F., Manni, A. Cancer Res. (2005) [Pubmed]
  12. Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity. Grossie, V.B., Ota, D.M., Ajani, J.A., Chang, T.H., Patenia, D., Nishioka, K. Cancer Res. (1989) [Pubmed]
  13. Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos. Jacoby, R.F., Cole, C.E., Tutsch, K., Newton, M.A., Kelloff, G., Hawk, E.T., Lubet, R.A. Cancer Res. (2000) [Pubmed]
  14. Alterations in bone marrow and blood mononuclear cell polyamine and methylglyoxal bis(guanylhydrazone) levels: phase I evaluation of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) treatment of human hematological malignancies. Maddox, A.M., Freireich, E.J., Keating, M.J., Haddox, M.K. Cancer Res. (1988) [Pubmed]
  15. Growth regulatory effects of cyclic AMP and polyamine depletion are dissociable in cultured mouse lymphoma cells. McConlogue, L.C., Marton, L.J., Coffino, P. J. Cell Biol. (1983) [Pubmed]
  16. Isolation of cloned cDNA encoding mammalian ornithine decarboxylase. Kahana, C., Nathans, D. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  17. The role of polyamine biosynthesis in hematopoietic precursor cell proliferation in mice. Niskanen, E., Kallio, A., McCann, P.P., Baker, D.G. Blood (1983) [Pubmed]
  18. Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors. Tutton, P.J., Barkla, D.H. Cancer Res. (1986) [Pubmed]
  19. Polyamines regulate expression of the neoplastic phenotype in mouse skin. Peralta Soler, A., Gilliard, G., Megosh, L., George, K., O'Brien, T.G. Cancer Res. (1998) [Pubmed]
  20. Luminal polyamines substitute for tissue polyamines in duodenal mucosal repair after stress in rats. Wang, J.Y., Johnson, L.R. Gastroenterology (1992) [Pubmed]
  21. RhoA inactivation inhibits cell migration but does not mediate the effects of polyamine depletion. Ray, R.M., Patel, A., Viar, M.J., McCormack, S.A., Zheng, Y., Tigyi, G., Johnson, L.R. Gastroenterology (2002) [Pubmed]
  22. Modulation of etoposide cytotoxicity and DNA strand scission in L1210 and 8226 cells by polyamines. Dorr, R.T., Liddil, J.D., Gerner, E.W. Cancer Res. (1986) [Pubmed]
  23. Differential effects of polyamine homologues on the prevention of DL-alpha-difluoromethylornithine-mediated inhibition of malignant cell growth and normal immune response. Singh, A.B., Thomas, T.J., Thomas, T., Singh, M., Mann, R.A. Cancer Res. (1992) [Pubmed]
  24. Polyamines as mediators of the effect of prolactin and growth hormone on the growth of N-nitroso-N-methylurea-induced rat mammary tumor cultured in vitro in soft agar. Manni, A., Wright, C. J. Natl. Cancer Inst. (1985) [Pubmed]
  25. Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil. Nigro, N.D., Bull, A.W., Boyd, M.E. J. Natl. Cancer Inst. (1986) [Pubmed]
  26. Polyamine involvement in the growth of hormone-responsive and -resistant human breast cancer cells in culture. Glikman, P., Manni, A., Demers, L., Bartholomew, M. Cancer Res. (1989) [Pubmed]
  27. Effects of inhibitors of polyamine biosynthesis on the growth and melanogenesis of murine melanoma cells. Käpyaho, K., Sinervirta, R., Jänne, J. Cancer Res. (1985) [Pubmed]
  28. Modulation of the tissue disposition of methylglyoxal bis(guanylhydrazone) in mice by polyamine depletion and by polyamine administration. Kallio, A., Seppänen, P., Alhonen-Hongisto, L., Jänne, J. Cancer Res. (1983) [Pubmed]
  29. Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide. Bauer, P.M., Buga, G.M., Ignarro, L.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  30. Induction of ornithine decarboxylase activity is a necessary step for mitogen-activated protein kinase kinase-induced skin tumorigenesis. Feith, D.J., Bol, D.K., Carboni, J.M., Lynch, M.J., Sass-Kuhn, S., Shoop, P.L., Shantz, L.M. Cancer Res. (2005) [Pubmed]
  31. Chemoprevention of mouse colon tumors with difluoromethylornithine during and after carcinogen treatment. Tempero, M.A., Nishioka, K., Knott, K., Zetterman, R.K. Cancer Res. (1989) [Pubmed]
  32. Phase I trial and pharmacokinetic studies of alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis. Abeloff, M.D., Slavik, M., Luk, G.D., Griffin, C.A., Hermann, J., Blanc, O., Sjoerdsma, A., Baylin, S.B. J. Clin. Oncol. (1984) [Pubmed]
  33. Difluoromethylornithine, an effective new treatment of Gambian trypanosomiasis. Results in five patients. Taelman, H., Schechter, P.J., Marcelis, L., Sonnet, J., Kazyumba, G., Dasnoy, J., Haegele, K.D., Sjoerdsma, A., Wery, M. Am. J. Med. (1987) [Pubmed]
  34. Protein kinase Cdelta-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression. Wheeler, D.L., Reddig, P.J., Dreckschmidt, N.E., Leitges, M., Verma, A.K. Oncogene (2002) [Pubmed]
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