Fluoropyrimidine (antimetabolite)

Fluoropyrimidines are a class of antimetabolite chemotherapy agents that interfere with the synthesis and function of nucleic acids, the molecules (DNA and RNA) that cells need to divide. Chemically, they resemble the natural pyrimidine base uracil, which allows them to be taken up by cellular enzymes that normally process uracil-based building blocks, after which the drug is metabolized to disrupt DNA replication and RNA processing. A central action is inhibition of thymidylate synthase, an enzyme required to make one of the four DNA building blocks; blocking it starves dividing cells of this building block and halts DNA synthesis. Because cancer cells divide more frequently than most normal tissues, they are disproportionately affected by this disruption, though rapidly renewing normal tissues such as the lining of the gut and bone marrow are also sensitive, which underlies much of the toxicity profile of this class. Fluoropyrimidines have broad relevance across many solid tumor types, often combined with other cytotoxic or targeted agents. Some fluoropyrimidines are administered as oral prodrugs, inactive compounds that are converted into the active drug within the body, which is intended to improve convenience and, in some cases, to concentrate drug activation preferentially within tumor tissue.