Folate Antagonists: Toward Improving the Therapeutic Index and Development of New Analogs

The folate antagonists are an important class of therapeutic compounds use as antiinfective, antineoplastic, and antiinflammatory drugs. In order to utilize new strategies or to develop new drugs targeted to preventing or to eradicating drug resistance, a detailed understanding of resistant mechanisms in tumor cells from patients is necessary.

[1]  G. Hitchings,et al.  Inhibitor binding analysis of dihydrofolate reductases from various species. , 1965, Molecular pharmacology.

[2]  J. Bertino,et al.  Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. , 1978, The Journal of biological chemistry.

[3]  B. Schweitzer,et al.  Amplification of a polymorphic dihydrofolate reductase gene expressing an enzyme with decreased binding to methotrexate in a human colon carcinoma cell line, HCT-8R4, resistant to this drug. , 1989, The Journal of biological chemistry.

[4]  K. Cowan,et al.  A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates. , 1984, The Journal of biological chemistry.

[5]  James T. Lin,et al.  Trimetrexate: a second generation folate antagonist in clinical trial. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  S. Rodenhuis,et al.  Development of an assay system for the detection and classification of methotrexate resistance in fresh human leukemic cells. , 1986, Cancer research.

[7]  J. Bertino,et al.  Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemic lymphoblast CCRF-CEM cell lines. , 1985, Cancer research.

[8]  J. Bertino,et al.  Detection of a single base mutation in the human dihydrofolate reductase gene from a methotrexate-resistant cell line using the polymerase chain reaction. , 1989, Cancer communications.

[9]  J. Shelhamer,et al.  Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. , 1987, The New England journal of medicine.

[10]  A. Levinson,et al.  Isolation and expression of an altered mouse dihydrofolate reductase cDNA. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Bertino,et al.  Inherent resistance of human squamous carcinoma cell lines to methotrexate as a result of decreased polyglutamylation of this drug. , 1989, Cancer research.

[12]  J. Bertino,et al.  Uptake and efficacy of trimetrexate (TMQ, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline), a non-classical antifolate in methotrexate-resistant leukemia cells in vitro. , 1984, Biochemical pharmacology.

[13]  J. Bertino,et al.  Carboxypeptidase G2 enhances trimetrexate cytotoxicity in CCRF-CEM cell lines sensitive and resistant to methotrexate. , 1989, Advances in enzyme regulation.

[14]  Stark Gr.  DNA amplification in drug resistant cells and in tumours. , 1986 .

[15]  G. Curt,et al.  Polyglutamation of methotrexate. Is methotrexate a prodrug? , 1985, The Journal of clinical investigation.

[16]  James T. Lin,et al.  Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug. , 1988, Cancer research.

[17]  R. Schimke.  Gene amplification in cultured animal cells , 1984, Cell.

[18]  D. W. Fry,et al.  Biochemical pharmacology of the lipophilic antifolate, trimetrexate. , 1984, Advances in enzyme regulation.

[19]  T. Tlsty,et al.  UV radiation facilitates methotrexate resistance and amplification of the dihydrofolate reductase gene in cultured 3T6 mouse cells , 1984, Molecular and cellular biology.