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

DDATHF     (2S)-2-[[4-[2-(4-amino-2-oxo- 3,5,7...

Synonyms: Lometrexol, DATHF, CHEMBL142806, SureCN9045915, SureCN10067961, ...
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 DDATHF


High impact information on DDATHF


Chemical compound and disease context of DDATHF

  • However, HX increased the protective effect of DDATHF from ICI D1694 toxicity, had no effect on the CB3717-DDATHF interaction, and reduced the protective effect of DDATHF on FdUrd toxicity [7].
  • These data indicated that a deficiency in dietary folic acid in mice caused increased hepatic retention of radioactivity and sustained plasma concentrations of DDATHF which are probably responsible for the observed toxicity of DDATHF in mice [8].

Biological context of DDATHF


Anatomical context of DDATHF


Associations of DDATHF with other chemical compounds

  • 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 [4].
  • The transport properties of DDATHF were also studied in a mutant cell line (CEM/MTX), resistant to MTX based on impaired drug transport [6].
  • Compound 1 was found to be a good substrate for partially purified mouse liver folypolyglutamate synthetase (FPGS), with a Michaelis constant (Km = 15 microM) comparable to that reported for the reduced folate substrate (6S)-5,6,7,8-tetrahydropteroyl-L-glutamic acid and for (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid (DDATHF) [9].
  • Indeed this thiazole was over 4 times more active in the MCF-7 cell line than the clinically investigated compound 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF) [14].
  • In a medium containing 2.27 microM folic acid the DDATHF IC50 values were 50 nm on OVCAR3, 500 nM on SW626 and 1000 nM on IGROV1 [3].

Gene context of DDATHF


Analytical, diagnostic and therapeutic context of DDATHF


  1. Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate. Li, W.W., Tong, W.P., Bertino, J.R. Clin. Cancer Res. (1995) [Pubmed]
  2. Enhancement of antineoplastic activity of 5-fluorouracil in mice bearing colon 38 tumor by (6R)5,10-dideazatetrahydrofolic acid. Pizzorno, G., Davis, S.J., Hartigan, D.J., Russello, O. Biochem. Pharmacol. (1994) [Pubmed]
  3. Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro. Sen, S., Erba, E., D'Incalci, M., Bottero, F., Canevari, S., Tomassetti, A. Br. J. Cancer (1996) [Pubmed]
  4. Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 function. Bronder, J.L., Moran, R.G. Cancer Res. (2002) [Pubmed]
  5. Induction of HL-60 leukemia cell differentiation by the novel antifolate 5,10-dideazatetrahydrofolic acid. Sokoloski, J.A., Beardsley, G.P., Sartorelli, A.C. Cancer Res. (1989) [Pubmed]
  6. 5,10-Dideazatetrahydrofolic acid (DDATHF) transport in CCRF-CEM and MA104 cell lines. Pizzorno, G., Cashmore, A.R., Moroson, B.A., Cross, A.D., Smith, A.K., Marling-Cason, M., Kamen, B.A., Beardsley, G.P. J. Biol. Chem. (1993) [Pubmed]
  7. 5,10-Dideazatetrahydrofolic acid reduces toxicity and deoxyadenosine triphosphate pool, expansion in cultured L1210 cells treated with inhibitors of thymidylate synthase. Chong, L.K., Tattersall, M.H. Biochem. Pharmacol. (1995) [Pubmed]
  8. Whole-body autoradiographic disposition and plasma pharmacokinetics of 5,10-dideazatetrahydrofolic acid in mice fed folic acid-deficient or regular diets. Pohland, R.C., Alati, T., Lantz, R.J., Grindey, G.B. Journal of pharmaceutical sciences. (1994) [Pubmed]
  9. (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydrofolate and 6(R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithine as potential antifolates and antitumor agents. Rosowsky, A., Forsch, R.A., Moran, R.G. J. Med. Chem. (1989) [Pubmed]
  10. Synthesis and antifolate activity of 5-methyl-5,10-dideaza analogues of aminopterin and folic acid and an alternative synthesis of 5,10-dideazatetrahydrofolic acid, a potent inhibitor of glycinamide ribonucleotide formyltransferase. Piper, J.R., McCaleb, G.S., Montgomery, J.A., Kisliuk, R.L., Gaumont, Y., Thorndike, J., Sirotnak, F.M. J. Med. Chem. (1988) [Pubmed]
  11. Mechanism of cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cells in vitro and modulation of the drug activity by folic or folinic acid. Erba, E., Sen, S., Sessa, C., Vikhanskaya, F.L., D'Incalci, M. Br. J. Cancer (1994) [Pubmed]
  12. A comparison of the effects of nine folate analogs on early and late murine hematopoietic progenitor cells in vitro. Strømhaug, A., Warren, D.J. Cancer Chemother. Pharmacol. (2000) [Pubmed]
  13. Role of membrane-associated folate binding protein in the cytotoxicity of antifolates in KB, IGROV1, and L1210A cells. Schultz, R.M., Andis, S.L., Shackelford, K.A., Gates, S.B., Ratnam, M., Mendelsohn, L.G., Shih, C., Grindey, G.B. Oncol. Res. (1995) [Pubmed]
  14. Thienyl and thiazolyl acyclic analogues of 5-deazatetrahydrofolic acid. Hodson, S.J., Bigham, E.C., Duch, D.S., Smith, G.K., Ferone, R. J. Med. Chem. (1994) [Pubmed]
  15. Mechanisms of acquired resistance to methotrexate in a human squamous carcinoma cell line of the head and neck, exposed to different treatment schedules. van der Laan, B.F., Jansen, G., Kathmann, I., Schornagel, J.H., Hordijk, G.J. Eur. J. Cancer (1991) [Pubmed]
  16. Induction of HL-60 leukemia cell differentiation by tetrahydrofolate inhibitors of de novo purine nucleotide biosynthesis. Sokoloski, J.A., Beardsley, G.P., Sartorelli, A.C. Cancer Chemother. Pharmacol. (1991) [Pubmed]
  17. Evidence for a relationship between intracellular GTP levels and the induction of HL-60 leukemia cell differentiation by 5,10-dideazatetrahydrofolic acid (DDATHF). Sokoloski, J.A., Pizzorno, G., Beardsley, G.P., Sartorelli, A.C. Oncol. Res. (1993) [Pubmed]
  18. Synthesis and biological activity of acyclic analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid. Shih, C., Gossett, L.S., Worzalla, J.F., Rinzel, S.M., Grindey, G.B., Harrington, P.M., Taylor, E.C. J. Med. Chem. (1992) [Pubmed]
  19. Bioanalysis of the investigational anti-tumour drug 5,10-dideaza-5,6,7,8-tetrahydrofolic acid by high-performance liquid chromatography with ultraviolet detection. van Tellingen, O., Sips, J.H., Beijnen, J.H., Schornagel, J.H., Nooyen, W.J. J. Chromatogr. (1992) [Pubmed]
WikiGenes - Universities