Fluorouracil

Also Known As: Fluorouracil, Adrucil, Carac, Efudix, Efudex, Fluoroplex, 5-FU

Fluorouracil (5-FU or f5U) (sold under the brand names Adrucil, Carac, Efudix, Efudex and Fluoroplex) is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called antimetabolites. It is typically administered with leucovorin.

The chemotherapy agent 5-FU, which has been used against cancer for about 40 years, acts in several ways, but principally as a thymidylate synthase inhibitor. Interrupting the action of this enzyme blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication. Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) into thymidine monophosphate (dTMP). Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via thymineless death.[1]

Like many anti-cancer drugs, 5-FU's effects are felt system wide but fall most heavily upon rapidly dividing cells that make heavy use of their nucleotide synthesis machinery, such as cancer cells, but also other cells in parts of the body that are rapidly dividing, for example, the cells lining the digestive tract.

Some of its principal uses are in colorectal cancer, and pancreatic cancer, in which it has been the established form of chemotherapy for decades (platinum-containing drugs approved for human use in the US since 1978 are also very well established). It is sometimes used in the treatment of inflammatory breast cancer, an especially aggressive form of breast cancer.

5-FU is used in ophthalmic surgery, specifically to augment trabeculectomy (an operation performed to lower the intraocular pressure in patients with glaucoma) in patients deemed to be at high risk for failure. 5-FU acts as an anti-scarring agent in this regard, since excessive scarring at the trabeculectomy site is the main cause for failure of the surgery.

Fluorouracil can be used topically (as a cream) for treating actinic (solar) keratoses and some types of basal cell carcinomas of the skin. It is often referred to by its trade names Efudex, Carac or Fluoroplex.

Due to fluorouracil's toxicity and the fact that it can be manufactured using the same reaction as uracil, its precursor, 5-fluoroorotic acid, is commonly used in laboratories to screen against organisms capable of synthesizing uracil.

It is a key component in tegafur-uracil.

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