Fluorouracil

Fluorouracil is a fluorinated pyrimidine antimetabolite that disrupts nucleic-acid synthesis. It is used against several cancers and for certain precancerous skin conditions.

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Thymidylate synthase: An enzyme that converts deoxyuridine monophosphate into deoxythymidine monophosphate, a DNA building block. Fluorouracil’s active metabolite inhibits this enzyme, restricting thymidine available for DNA synthesis.
Colorectal cancer: A cancer arising in the colon or rectum. Fluorouracil is a longstanding component of combination regimens for this cancer.
Pyrimidine: A six-membered aromatic nitrogen-containing ring that forms the core of several biological bases. Fluorouracil is a modified pyrimidine that resembles natural nucleic-acid building blocks.
Fluorouracil toxicity: Adverse effects caused by fluorouracil exposure, ranging from common tissue injury to severe toxicity. Its toxicities reflect damage to rapidly dividing tissues and variable drug clearance.
FdUMP: A fluorouracil metabolite that forms a stable inhibitory complex with thymidylate synthase and folate. This metabolite directly drives fluorouracil’s blockade of thymidylate production.
Pancreatic cancer: A malignant tumor arising in the pancreas. Fluorouracil appears in combination treatments for some patients with this cancer.
Antimetabolite: A substance that resembles a natural metabolite and disrupts processes that use it. This drug class captures how fluorouracil impersonates pyrimidine metabolites.
Hand-foot syndrome: A treatment-related skin reaction causing redness, swelling, pain, or peeling on palms and soles. This characteristic adverse effect can limit systemic fluorouracil treatment.
FUTP: A fluorouracil nucleotide metabolite that can be incorporated into RNA. Its incorporation disrupts RNA processing and function, complementing DNA-directed effects.
Actinic keratosis: A rough, sun-damaged skin lesion that can progress to cutaneous squamous cell carcinoma. Topical fluorouracil is used to treat these precancerous lesions.