Disease relevance of HSDB 7316

• A Phase I Study of Pemetrexed (ALIMTA) and Cyclophosphamide in Patients with Locally Advanced or Metastatic Breast Cancer [1].
• Pemetrexed (ALIMTA, MTA) is a novel thymidylate synthase (TS) inhibitor and has shown activity against colon cancer, mesothelioma and nonsmall-cell lung cancer [2].
• Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression [2].
• Pemetrexed (Alimta) in small cell lung cancer [3].
• The role of Alimta in the treatment of malignant pleural mesothelioma: an overview of preclinical and clinical trials [4].

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

• Search terms included pemetrexed, Alimta, MTA, multitargeted antifolate, LY231514, mesothelioma, MPM, non-small cell lung cancer, NSCLC, breast cancer, and pancreatic cancer [10].
• Gemcitabine/Alimta in locally advanced or metastatic non-small-cell lung cancer [11].
• Pemetrexed disodium (ALIMTA), "pemetrexed") is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck [12].

Biological context of HSDB 7316

• We next analyzed the effects of the anti-Wnt2 antibody and of Alimta on MPM cell proliferation [8].

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, http://www.lilly.com), bortezomib (Velcade; Millennium Pharmaceuticals, Inc., Cambridge, MA, http://www.mlnm.com), and cetuximab (Erbitux; ImClone Systems, Inc., New York, NY, http://www.imclone.com) [16].

Gene context of HSDB 7316

• In cell culture, moderate cross-resistance (about 2-fold) was observed to 1-ss-D-arabinofuranosylcytosine (ara-C), 2-chloro-2'deoxyadenosine (CdA), LY231514 (ALIMTA), and cisplatin (CDDP), and pronounced cross-resistance (>23-fold) to 2',2'-difluorodeoxyuridine (dFdU) and 2',2'-difluorodeoxyguanosine (dFdG) [17].
• Thymidilate Synthase Inhibitors: The Role of ALIMTA in Non-Small Cell Lung Cancer [18].

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].

References