Fluoropyrimidine

Pyrimidine_2D_numbers

Fluorouracil2DACS

Capecitabine

5-Fluorodeoxyuridine_monophosphate

Fluoropyrimidine

Fluoropyrimidines are a class of antimetabolite drugs that are commonly used in the treatment of various types of cancer. These compounds are analogs of the naturally occurring pyrimidines, which are essential components of nucleic acids. By mimicking these natural substances, fluoropyrimidines interfere with DNA and RNA synthesis, thereby inhibiting the growth and proliferation of cancer cells.

Mechanism of Action

Fluoropyrimidines exert their effects primarily through the inhibition of the enzyme thymidylate synthase, which is crucial for the synthesis of thymidine monophosphate (dTMP), a nucleotide required for DNA replication. The inhibition of thymidylate synthase leads to a depletion of dTMP, resulting in DNA damage and cell death. Additionally, fluoropyrimidines can be incorporated into RNA, disrupting its normal function and further contributing to cytotoxicity.

Common Fluoropyrimidines

The most widely used fluoropyrimidines in clinical practice include:

• 5-Fluorouracil (5-FU)
• Capecitabine
• Tegafur

5-Fluorouracil (5-FU)

5-Fluorouracil is one of the oldest and most commonly used fluoropyrimidines. It is often administered intravenously and is used to treat a variety of cancers, including colorectal cancer, breast cancer, and gastric cancer.

Capecitabine

Capecitabine is an oral prodrug of 5-FU. It is converted to 5-FU in the body, allowing for more convenient administration. Capecitabine is used to treat colorectal cancer and breast cancer.

Tegafur

Tegafur is another prodrug of 5-FU, often combined with other agents such as uracil or gimeracil to enhance its efficacy and reduce side effects. It is used in the treatment of various solid tumors.

Side Effects

The use of fluoropyrimidines is associated with several side effects, which can vary depending on the specific drug and the regimen used. Common side effects include:

• Myelosuppression
• Gastrointestinal toxicity
• Hand-foot syndrome
• Cardiotoxicity

Pharmacogenomics

The efficacy and toxicity of fluoropyrimidines can be influenced by genetic variations in enzymes involved in their metabolism. For example, polymorphisms in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), can lead to severe toxicity in patients treated with 5-FU or capecitabine. Genetic testing for DPYD variants can help identify patients at risk and guide dose adjustments.

Related Pages

• Antimetabolite
• Thymidylate synthase
• DNA replication
• RNA
• Colorectal cancer
• Breast cancer
• Gastric cancer
• Myelosuppression
• Hand-foot syndrome
• Cardiotoxicity
• Pharmacogenomics