Cellular pharmacology of MTA: a correlation of MTA-induced cellular toxicity and in vitro enzyme inhibition with its effect on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells
| Autor: | V J, Chen, J R, Bewley, S L, Andis, R M, Schultz, P W, Iversen, C, Shih, L G, Mendelsohn, D E, Seitz, J L, Tonkinson |
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| Rok vydání: | 1999 |
| Předmět: |
Antimetabolites
Antineoplastic Guanine Deoxyribonucleotides Pemetrexed Thiophenes Thymidylate Synthase Ribonucleotides Nucleoside-Triphosphatase Acid Anhydride Hydrolases Folic Acid Methotrexate Glutamates Nucleoside-Diphosphate Kinase Quinazolines Tumor Cells Cultured Folic Acid Antagonists Humans Thymine Nucleotides Enzyme Inhibitors Tetrahydrofolates |
| Zdroj: | Seminars in oncology. 26(2 Suppl 6) |
| ISSN: | 0093-7754 |
| Popis: | The mechanism of action of an antifolate may be investigated using a variety of experimental methods. These include experiments in a cell culture setting to observe possible protection against drug effects afforded by the end products of metabolic pathways, assessing the activity of purified target enzymes in the presence of the antifolate, and, finally, the measurement of drug effects on intracellular folate and nucleoside triphosphate pools. The current discussion is focused on studies using CCRF-CEM leukemia cells that were designed to compare and contrast mechanisms of action of the antifolates methotrexate, which is primarily a dihydrofolate reductase inhibitor, raltitrexed, a thymidylate synthase inhibitor, LY309887, a glycinamide ribonucleotide formyltransferase inhibitor, and MTA (multitargeted antifolate), which is a novel antifolate antimetabolite. The results of these studies support the hypothesis that MTA affects multiple enzymatic targets and has a distinct mechanism of action from methotrexate, raltitrexed, and LY309887. |
| Databáze: | OpenAIRE |
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