Abstract
The antifolates remain a topic of continuing fascination to pharmacologists. This in-terest is not entirely theoretical. Recent years have seen two new antifolate drugs approved for marketing: trimetrexate (Neutrexin), a lipophilic inhibitor of dihydrofolate reductase (DHFR) for treatment of the life-threatening fungal infection, Pneumocystis carinii pneumonia; and the thymidylate synthase (TS) inhibitor, raltitrexed (Tomudex), for colorectal cancer. In addition to their importance as drugs, however, the antifolates have taught us some important lessons about general principles of pharmacology—how to use drugs optimally, how to design improved selectivity into next-generation compounds, how cells become drug resistant and how to use biochemical modulation approaches. They have also been valuable probes for exploring basic biology. These points will be made using 10 examples of topics in antifolate pharmacology that have sparked major debates over the years. Several of these areas will be dealt with very briefly, because they are covered in more detail in subsequent chapters. The final section touches on some unanswered questions, which are areas of current debate, and which are likely to be the focus of ongoing research.
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Jackson, R.C. (1999). Antifolate Drugs. In: Jackman, A.L. (eds) Antifolate Drugs in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-725-3_1
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DOI: https://doi.org/10.1007/978-1-59259-725-3_1
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4757-4521-4
Online ISBN: 978-1-59259-725-3
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