|1.||Gao, F: 2 articles (08/2000 - 08/2000)|
|2.||Zhao, R: 2 articles (08/2000 - 08/2000)|
|3.||Goldman, I D: 2 articles (08/2000 - 08/2000)|
|4.||Boger, Dale L: 1 article (05/2003)|
|5.||Olson, Arthur J: 1 article (05/2003)|
|6.||Li, Chenglong: 1 article (05/2003)|
|7.||Zhang, Yan: 1 article (05/2003)|
|8.||Benkovic, Stephen J: 1 article (05/2003)|
|9.||Desharnais, Joel: 1 article (05/2003)|
|10.||Tavassoli, Ali: 1 article (05/2003)|
01/01/1991 - "Previous studies from our laboratory have shown that DDATHF is an effective inducer of the maturation of HL-60 promyelocytic leukemia. "
09/01/1989 - "Incubation of HL-60 promyelocytic leukemia cells with 5 x 10(-8) to 10(-5) M DDATHF resulted in a marked inhibition of growth after 48 h, with a complete cessation of cellular replication by day 4. Cell cycle analyses of DDATHF-treated HL-60 cells demonstrated an initial block in early S phase by day 3 followed by an accumulation of cells in the G1 and G2 + M phases of the cell cycle. "
09/01/1989 - "Induction of HL-60 leukemia cell differentiation by the novel antifolate 5,10-dideazatetrahydrofolic acid."
01/01/1991 - "The role of an mFBP in the uptake of DDATHF was suggested from observations that (a) the mFBP showed a very high binding affinity for DDATHF, (b) murine and human leukemia cells expressing an mFBP were highly sensitive to growth inhibition by DDATHF, and (c) protection against this growth inhibition could be achieved using folic acid rather than reduced folate compounds."
01/01/1996 - "Lometrexol and LY309887 were potent cytotoxic compounds against the human leukemia cell line CCRF-CEM with IC50's of 2.9 nM and 9.9 nM, respectively. "
05/27/2003 - "Moreover, compound 1 is a potent inhibitor of tumor cell proliferation (IC(50) = 16 nM, CCRF-CEM), which represents a 10-fold improvement over Lometrexol, a GAR Tfase inhibitor that has been in clinical trials. "
07/21/1993 - "DDATHF has an unusual pattern of toxicity with repetitive dosing, and humans with advanced cancer are considerably more sensitive than would be predicted from previous animal studies. "
01/01/1996 - "A comparison of the efficacy and toxicity of lometrexol in C3H mammary tumor-bearing mice showed that in mice on LFD, lometrexol treatment produced a delayed toxicity with an LD50 of 0.1-0.3 mg/kg, a 3000-fold increase in lethality compared to SD mice. "
01/01/1996 - "Consistent with these changes in liver FPGS, mice injected i.v. with a single dose of lometrexol accumulated significantly more drug in liver and tumors of LFD animals compared to SD mice. "
08/01/1995 - "After correction for the intrinsic inhibitory activity of the parent DDATHF analog as an inhibitor of the target enzyme, the first-order rate constants for FPGS were found to be predictive of the potency of tumor cell growth inhibition for most of the compounds in this structural series."
|3.||Hepatocellular Carcinoma (Hepatoma)
09/01/1995 - "A subline of H35 hepatoma cells (H35D cells) that have been made resistant to 5,10-dideazatetrahydrofolate exhibits an increase in gamma-glutamyl hydrolase (GH) activity. "
05/15/1993 - "A subline of H35 hepatoma cells has been developed which exhibits 80-fold resistance to 5,10-dideazatetrahydrofolate, an antifolate which inhibits glycinamideribonucleotide transformylase. "
05/01/1988 - "H35 hepatoma cells resistant to methotrexate (100-fold) as a result of a transport defect are 40-fold resistant to 5,10-dideazatetrahydrofolate suggesting that this analogue enters hepatoma cells at least in part by the reduced folate coenzyme-methotrexate transport system. "
05/01/1988 - "The presence of low concentrations of the lipophilic dihydrofolate reductase inhibitors metoprine or trimetrexate, which cause little inhibition in the growth of cultured hepatoma cells in combination with weakly inhibiting concentrations of 5,10-dideazatetrahydrofolate, exhibit greater activity than would be predicted by the activity of the individual components. "
01/01/1989 - "Treatment of H35 hepatoma cells with the lipid soluble dihydrofolate reductase inhibitors metoprine and trimetrexate cause a nearly 10-fold increase in the toxicity of the antipyrimidine folate analogue PDDF and the antipurine folate analogue DDATHF. "
09/15/2002 - "Cell cycle progression into and through S phase was slowed by DDATHF, but both p53 +/+ and -/- human colon carcinoma cells entered and completed one S phase in the presence of drug. "
09/15/2002 - "We conclude that carcinoma cells are killed equally well by DDATHF and related compounds whether or not the p53 pathway is intact and that the utility of GART inhibitors would not be limited to p53-negative tumors."
03/15/1994 - "The growth of multicellular tumor spheroids of WiDr human colon carcinoma was inhibited by the GAR TFase inhibitors 5-deazaacyclotetrahydrofolate (5-DACTHF), its 2'-fluoro, 3'-fluoro, 10-deaza, and 10-thia analogs as well as 5,10-dideazatetrahydrofolate, but none of the compounds caused spheroid regressions. "
02/01/1996 - "Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro."
02/01/1996 - "Lometrexol (5,10-dideazatetrahydrofolic acid; DDATHF), is a specific inhibitor of glycinamideribonucleosyl (GAR) transformylase with anti-tumour activity in murine and human carcinomas. "
|5.||Precursor Cell Lymphoblastic Leukemia-Lymphoma (Acute Lymphoblastic Leukemia)
|1.||Folic Acid (Vitamin M)
|6.||Folic Acid Antagonists
|7.||Tetrahydrofolate Dehydrogenase (Dihydrofolate Reductase)
|9.||Guanosine Triphosphate (GTP)
|10.||raltitrexed (D 1694)
|1.||Heterologous Transplantation (Xenotransplantation)