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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Synergistic interactions among antifolates.

Many cultured human cell lines show large synergistic cytotoxicity when an inhibitor of dihydrofolate reductase (EC is combined with an antifolate inhibitor of thymidylate synthase (EC 2. 1.1.45) or with an antifolate inhibitor of glycinamide ribonucleotide formyltransferase (EC These synergistic interactions are dependent on medium folic acid concentration and are greatly enhanced by increasing folic acid levels. Synergism is seen only when the thymidylate synthase or glycinamide ribonucleotide formyltransferase inhibitor is polyglutamylatable. Here we will briefly outline the rigorous method used to quantitate synergistic interactions by measuring alpha, a response surface-based parameter; give examples of synergistic interactions from the current literature; and evaluate proposals offered to explain the metabolic basis of the synergism.[1]


  1. Synergistic interactions among antifolates. Kisliuk, R.L. Pharmacol. Ther. (2000) [Pubmed]
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