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Chemical Compound Review

Rolazar     disodium(2R)-2-[[4-[2-(4- amino-2-oxo-3,5...

Synonyms: Tifolar, Alimta, Bio-0078, cc-282, CHEMBL1200373, ...
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Disease relevance of HSDB 7316


High impact information on HSDB 7316

  • Endogenous folate pools were modestly reduced but polyglutamate derivatives of DDATHF and ALIMTA (LY231514, MTA) were markedly decreased in these mutant cell lines [5].
  • Induction of thymidylate synthase expression inhibited Fas induction in response to RTX and Alimta, but not in response to 5-FU [6].
  • In contrast, in the two pairs of related human tumor cell lines (HCT-116 and HCT-116/N7 and A2780 and A2780/CP70) cells with functional p53 were more sensitive to Alimta- and raltitrexed-induced growth inhibition (P = 0.002) [7].
  • We then assessed the antiproliferative effects of the Wnt2 antibody and Alimta, one of the current standard treatments of MPM [8].
  • PURPOSE: The novel folate antimetabolite Alimta (pemetrexed disodium, LY231514) exhibits antitumor activity in a broad array of human malignancies and was recently found to enhance radiation-induced cell killing in vitro [9].

Chemical compound and disease context of HSDB 7316


Biological context of HSDB 7316


Associations of HSDB 7316 with other chemical compounds

  • Detailed studies were performed with the A2780 cell lines, and in the parental cells sensitivity to Alimta- and raltitrexed-induced cytotoxicity (clonogenic assay) was similar to the sensitivity determined in the sulphorhodamine B assay [7].
  • Palladium-catalyzed C-C coupling with diethyl 4-iodobenzoylglutamate led in one step via an unexpected redox reaction to the diethyl esters 9 of a series of 7-substituted derivatives of ALIMTA (LY231514, MTA), from which the target analogues 10 were readily prepared by saponification [13].
  • FDA drug approval summaries: pemetrexed (Alimta) [14].
  • Pemetrexed (Alimta, LY231514) demonstrates clinical activity in chemonaive patients with cervical cancer in a phase II single-agent trial [15].
  • Three drugs with promising activity in NSCLC are pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, IN,, bortezomib (Velcade; Millennium Pharmaceuticals, Inc., Cambridge, MA,, and cetuximab (Erbitux; ImClone Systems, Inc., New York, NY, [16].

Gene context of HSDB 7316


Analytical, diagnostic and therapeutic context of HSDB 7316

  • CONCLUSIONS: ALIMTA is active in a second-line setting in non-platinum-pretreated NSCLC patients progressing within 3 months of first-line chemotherapy [19].
  • ALIMTA was administered at 500 mg/m2 by 10-min intravenous infusion once every 21 days [19].
  • Treatment of head and neck and esophageal xenografts employing Alimta and concurrent ionizing radiation [20].
  • The present data suggest the potential clinical efficacy of combining Alimta administration with radiotherapy for Alimta-sensitive cells and indicate that further testing needs to be conducted to optimize the dosing schedule to enhance the interaction between the therapeutic agents [20].
  • DNA flow cytometry studies indicated that Alimta causes a build-up of cells near the G1/S interface after 24 hours of incubation [21].


  1. A Phase I Study of Pemetrexed (ALIMTA) and Cyclophosphamide in Patients with Locally Advanced or Metastatic Breast Cancer. Dittrich, C., Petruzelka, L., Vodvarka, P., Gneist, M., Janku, F., Kysela, T., Melemed, A., Latz, J., Simms, L., Krejcy, K. Clin. Cancer Res. (2006) [Pubmed]
  2. Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. Sigmond, J., Backus, H.H., Wouters, D., Temmink, O.H., Jansen, G., Peters, G.J. Biochem. Pharmacol. (2003) [Pubmed]
  3. Pemetrexed (Alimta) in small cell lung cancer. Socinski, M.A. Semin. Oncol. (2005) [Pubmed]
  4. The role of Alimta in the treatment of malignant pleural mesothelioma: an overview of preclinical and clinical trials. Hanauske, A.R. Lung Cancer (2004) [Pubmed]
  5. Molecular analysis of murine leukemia cell lines resistant to 5, 10-dideazatetrahydrofolate identifies several amino acids critical to the function of folylpolyglutamate synthetase. Zhao, R., Titus, S., Gao, F., Moran, R.G., Goldman, I.D. J. Biol. Chem. (2000) [Pubmed]
  6. The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptosis in response to antimetabolites. Longley, D.B., Allen, W.L., McDermott, U., Wilson, T.R., Latif, T., Boyer, J., Lynch, M., Johnston, P.G. Clin. Cancer Res. (2004) [Pubmed]
  7. The impact of p53 status on cellular sensitivity to antifolate drugs. Lu, X., Errington, J., Curtin, N.J., Lunec, J., Newell, D.R. Clin. Cancer Res. (2001) [Pubmed]
  8. Wnt2 as a new therapeutic target in malignant pleural mesothelioma. Mazieres, J., You, L., He, B., Xu, Z., Twogood, S., Lee, A.Y., Reguart, N., Batra, S., Mikami, I., Jablons, D.M. Int. J. Cancer (2005) [Pubmed]
  9. Radiosensitization by pemetrexed of human colon carcinoma cells in different cell cycle phases. Bischof, M., Huber, P., Stoffregen, C., Wannenmacher, M., Weber, K.J. Int. J. Radiat. Oncol. Biol. Phys. (2003) [Pubmed]
  10. Pemetrexed: a multitargeted antifolate. Rollins, K.D., Lindley, C. Clinical therapeutics. (2005) [Pubmed]
  11. Gemcitabine/Alimta in locally advanced or metastatic non-small-cell lung cancer. Ettinger, D.S. Oncology (Williston Park, N.Y.) (2000) [Pubmed]
  12. Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Hanauske, A.R., Chen, V., Paoletti, P., Niyikiza, C. Oncologist (2001) [Pubmed]
  13. A new route to 7-substituted derivatives of n-[4-(2-[2-amino-3,4-dihydro-4-oxo-7H-pyrrolo(2,3-d)pyrimidin-5-yl]ethyl)benzoyl]-L-glutamic acid [ALIMTA (LY231514, MTA)]. Taylor, E.C., Liu, B. J. Org. Chem. (2001) [Pubmed]
  14. FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, R.M., Johnson, J.R., Pazdur, R. Oncologist (2004) [Pubmed]
  15. Pemetrexed (Alimta, LY231514) demonstrates clinical activity in chemonaive patients with cervical cancer in a phase II single-agent trial. Goedhals, L., van Wiyk, A.L., Smith, B.L., Fourie, S.J. Int. J. Gynecol. Cancer (2006) [Pubmed]
  16. Three emerging new drugs for NSCLC: pemetrexed, bortezomib, and cetuximab. Dubey, S., Schiller, J.H. Oncologist (2005) [Pubmed]
  17. Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits. Smid, K., Bergman, A.M., Eijk, P.P., Veerman, G., Ruiz van Haperen, V.W., van den Ijssel, P., Ylstra, B., Peters, G.J. Nucleosides Nucleotides Nucleic Acids (2006) [Pubmed]
  18. Thymidilate Synthase Inhibitors: The Role of ALIMTA in Non-Small Cell Lung Cancer. Scagliotti, G.V. Current oncology reports. (2004) [Pubmed]
  19. ALIMTA (pemetrexed disodium) as second-line treatment of non-small-cell lung cancer: a phase II study. Smit, E.F., Mattson, K., von Pawel, J., Manegold, C., Clarke, S., Postmus, P.E. Ann. Oncol. (2003) [Pubmed]
  20. Treatment of head and neck and esophageal xenografts employing Alimta and concurrent ionizing radiation. Mauceri, H.J., Seetharam, S., Salloum, R.M., Vokes, E.E., Weichselbaum, R.R. Int. J. Oncol. (2001) [Pubmed]
  21. Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Schultz, R.M., Dempsey, J.A. Anticancer Res. (2001) [Pubmed]
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