The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Methotrexate, (DL)-Isomer     2-[[4-[(2,4-diaminopteridin- 6-yl)methyl...

Synonyms: Prestwick_753, SureCN3712, AGN-PC-0CK8VG, TCMDC-123832, BSPBio_000210, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Amethopterin


Psychiatry related information on Amethopterin


High impact information on Amethopterin

  • Several variants resistant to 1.8 x 10(-4) M DL-methotrexate (MTX) have been isolated from the human cell lines HeLa BU25 and VA2-B by exposing them to progressively increasing concentrations of the drug [7].
  • This may be in part due to the MTAP-dependent salvage of adenine moieties from endogenously generated MTA, because the MTAP inhibitor 5'-chloro-5'-de- oxyformycin A potentiates the antipurine actions of MTX in some of these MTAP(+) lines [8].
  • The residual 7-OH-MTX tetraglutamate remained bound to a site with a molecular weight of approximately 25,000 to 35,000 as assessed by Bio-Gel P-60 analysis and could not be displaced by folic acid, 5-formyltetrahydrofolate, 7-OH-MTX, or the tetraglutamate of MTX [9].
  • 7-OH-MTX and MTX cytotoxicities were compared by clonogenic assay in agar and by their effects on cell growth [9].
  • We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy [3].

Chemical compound and disease context of Amethopterin


Biological context of Amethopterin

  • Third, 5-FU disrupted rRNA processing by a different mechanism from actinomycin D and methotrexate (MTX), suggesting that the inhibition was not just a consequence of cell death [12].
  • The doses effective in 50% inhibition of the cell proliferation (ED50 values) for EDX, MTX, and Cis-Pt were 0.001, 0.0043, and 1.08 microM, respectively [13].
  • Preincubation of rat-liver homogenates with 1.25-10 microM mAMSA reduced the formation of 7-OH-MTX by up to 73%. mAMSA appeared to inhibit MTX hydroxylation competitively, exhibiting a Ki of 3 microM [14].
  • 7-OH-MTX peak concentrations and AUC in bile and serum were reduced by 75% and the recovery of MTX as 7-OH-MTX in bile and urine decreased by 70%, whereas MTX pharmacokinetics remained unaltered [14].
  • The inhibition of methotrexate (MTX) biotransformation to 7-hydroxymethotrexate (7-OH-MTX) by 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA) was studied in bile-drained rats in vivo and in incubates of isolated rat hepatocytes and rat-liver homogenate in vitro [14].

Anatomical context of Amethopterin


Associations of Amethopterin with other chemical compounds

  • PURPOSE: To assess the efficacy, tolerability and safety of MTX-HSA (methotrexate (MTX) covalently linked to human serum albumin (HSA)) combined with cisplatin as first line therapy for advanced bladder cancer [19].
  • Intracarotid co-administration of MTX and 1-O-pentylglycerol (200 mm) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1-O-pentylglycerol (P<0.005) [20].
  • RESULTS: ADM, CDDP, CPM and VCR, but not MTX, induced death of HOS cells in a dose-dependent manner [5].
  • Infection was associated with duration of RA before admission and followup, comorbidity, extraarticular disease, mean cumulative dose of MTX, time taking steroids, and mean daily dose of D-penicillamine, by univariate analysis [21].
  • Transfection with HSV-tk revealed an increased sensitivity to GCV and CDDP and a decreased sensitivity to ADR and MTX [22].

Gene context of Amethopterin

  • In contrast, MTAP(-) cell lines, which cannot recycle purines from endogenous MTA, have a relatively high sensitivity to the antipurine actions of MTX, which is not modulated by 5'-chloro-5'-deoxyformycin A or exogenous MTA [8].
  • Etanercept was launched in the US in November 1998, for the treatment of moderate-to-severe RA in patients with inadequate responses to one or more DMARDs, or in combination with MTX in patients who do not respond adequately to MTX alone [306175] [23].
  • Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone [3].
  • To prove this possibility, we analyzed an MTX-resistant subline, CEM/MTX1500LV, in which the MTX-resistance conferring dihydrofolate reductase (DHFR) gene was amplified [24].
  • In sera from the mtx-treated RA-patients the expression of antibodies was reduced [25].

Analytical, diagnostic and therapeutic context of Amethopterin


  1. Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. Synold, T.W., Relling, M.V., Boyett, J.M., Rivera, G.K., Sandlund, J.T., Mahmoud, H., Crist, W.M., Pui, C.H., Evans, W.E. J. Clin. Invest. (1994) [Pubmed]
  2. Modulation of 5-fluorouracil metabolism and cytotoxicity by antimetabolite pretreatment in human colorectal adenocarcinoma HCT-8. Benz, C., Cadman, E. Cancer Res. (1981) [Pubmed]
  3. Temozolomide as salvage treatment in primary brain lymphomas. Reni, M., Zaja, F., Mason, W., Perry, J., Mazza, E., Spina, M., Bordonaro, R., Ilariucci, F., Faedi, M., Corazzelli, G., Manno, P., Franceschi, E., Pace, A., Candela, M., Abbadessa, A., Stelitano, C., Latte, G., Ferreri, A.J. Br. J. Cancer (2007) [Pubmed]
  4. Antifolate analogs: mechanism of action, analytical methodology, and clinical efficacy. Fleisher, M. Therapeutic drug monitoring. (1993) [Pubmed]
  5. Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma. Seki, K., Yoshikawa, H., Shiiki, K., Hamada, Y., Akamatsu, N., Tasaka, K. Cancer Chemother. Pharmacol. (2000) [Pubmed]
  6. Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. van Halm, V.P., Nurmohamed, M.T., Twisk, J.W., Dijkmans, B.A., Voskuyl, A.E. Arthritis Res. Ther. (2006) [Pubmed]
  7. Variable content of double minute chromosomes is not correlated with degree of phenotype instability in methotrexate-resistant human cell lines. Masters, J., Keeley, B., Gay, H., Attardi, G. Mol. Cell. Biol. (1982) [Pubmed]
  8. Gene deletion chemoselectivity: codeletion of the genes for p16(INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for chemotherapy. Chen, Z.H., Zhang, H., Savarese, T.M. Cancer Res. (1996) [Pubmed]
  9. Formation of 7-hydroxymethotrexate polyglutamyl derivatives and their cytotoxicity in human chronic myelogenous leukemia cells, in vitro. Fabre, G., Goldman, I.D. Cancer Res. (1985) [Pubmed]
  10. 7-Hydroxymethotrexate concentrations in serum and cerebrospinal fluid of children with acute lymphoblastic leukemia. Borsi, J.D., Sagen, E., Romslo, I., Slørdal, L., Moe, P.J. Cancer Chemother. Pharmacol. (1990) [Pubmed]
  11. Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists. Nielsen, H.J., Hammer, J.H. Med. Hypotheses (1992) [Pubmed]
  12. Effect of 5-fluorouracil combination therapy on RNA processing in human colonic carcinoma cells. Greenhalgh, D.A., Parish, J.H. Br. J. Cancer (1990) [Pubmed]
  13. Quantitation of the synergistic interaction of edatrexate and cisplatin in vitro. Chou, T.C., Tan, Q.H., Sirotnak, F.M. Cancer Chemother. Pharmacol. (1993) [Pubmed]
  14. Inhibition of 7-hydroxymethotrexate formation by amsacrine. Bremnes, R.M., Smeland, E., Willassen, N.P., Wist, E., Aarbakke, J. Cancer Chemother. Pharmacol. (1991) [Pubmed]
  15. DNA fragmentation, dATP pool elevation and potentiation of antifolate cytotoxicity in L1210 cells by hypoxanthine. Kwok, J.B., Tattersall, M.H. Br. J. Cancer (1992) [Pubmed]
  16. Role of neutrophils in indomethacin-induced gastric mucosal lesions in rats. Alican, I., Coşkun, T., Corak, A., Yeğen, B.C., Oktay, S., Kurtel, H. Inflamm. Res. (1995) [Pubmed]
  17. Synthesis and antitumor activity of pyrrolo[2,3-d]pyrimidine antifolates with a bridge chain containing a nitrogen atom. Aso, K., Hitaka, T., Yukishige, K., Ootsu, K., Akimoto, H. Chem. Pharm. Bull. (1995) [Pubmed]
  18. The effects of anticancer drugs on levels of nitric oxide and adrenomedullin. G??ler, E., Balat, A., Cekmen, M., Kilin??, M., Sivasli, E., Y??rekli, M., Duman, C. Turk. J. Pediatr. (2006) [Pubmed]
  19. Phase II study of MTX-HSA in combination with Cisplatin as first line treatment in patients with advanced or metastatic transitional cell carcinoma. Bolling, C., Graefe, T., Lübbing, C., Jankevicius, F., Uktveris, S., Cesas, A., Meyer-Moldenhauer, W.H., Starkmann, H., Weigel, M., Burk, K., Hanauske, A.R. Investigational new drugs. (2006) [Pubmed]
  20. Alkylglycerol opening of the blood-brain barrier to small and large fluorescence markers in normal and C6 glioma-bearing rats and isolated rat brain capillaries. Erdlenbruch, B., Alipour, M., Fricker, G., Miller, D.S., Kugler, W., Eibl, H., Lakomek, M. Br. J. Pharmacol. (2003) [Pubmed]
  21. Development, recurrence, and severity of infections in Mexican patients with rheumatoid arthritis. A nested case-control study. Hernández-Cruz, B., Cardiel, M.H., Villa, A.R., Alcocer-Varela, J. J. Rheumatol. (1998) [Pubmed]
  22. Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity. Van Dillen, I.J., Mulder, N.H., Meijer, C., Dam, W.A., Kamstra, E., De Vries, L., Meersma, G.J., Van der Zee, A.G., De Vries, E.F., Vaalburg, W., Hospers, G.A. Journal of chemotherapy (Florence, Italy) (2005) [Pubmed]
  23. Etanercept Immunex. Yung, R.L. Current opinion in investigational drugs (London, England : 2000) (2001) [Pubmed]
  24. Methylthioadenosine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells. Efferth, T., Miyachi, H., Drexler, H.G., Gebhart, E. Blood Cells Mol. Dis. (2002) [Pubmed]
  25. Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading. Roth, E.B., Stenberg, P., Book, C., Sjöberg, K. Clin. Exp. Rheumatol. (2006) [Pubmed]
  26. Clinical response following adjuvant Temozolomide in a patient with primary cerebral lymphoma. Strik, H.M., Spreer, A., Nagel, H., Jacob, S., Jung, W., Kitze, B., Bähr, M. Anticancer Res. (2004) [Pubmed]
  27. Effect of neutropenia on gastric mucosal integrity and mucosal nitric oxide synthesis in the rat. Tepperman, B.L., Vozzolo, B.L., Soper, B.D. Dig. Dis. Sci. (1993) [Pubmed]
WikiGenes - Universities