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Anti-Metabolites
The body processes food into materials that the body can use, i.e., metabolites, organic compounds such as vitamins and amino acids. These metabolites are necessary for the creation of proteins to be used in DNA creation. Anti-metabolites are chemically similar to metabolites so they are taken up in the cell in the same way but they cannot be used to produce DNA, effectively ending the cell cycle in the second phase.
There are three primary types of anti-metabolites.
Anti-folates – In the 1940s to 1950s, it was discovered that folic acid seemed to cause proliferation of childhood leukemia cells. Researchers developed an anti-folate that deprived selected enzymes of the folate needed to produce nucleic acids for DNA creation. This drug, methotrexate, FDA-approved in 1953, is still a primary building block of chemotherapeutic regimens. Alimta is an antifolate. Here is an abstract from an Israeli researcher on the molecular basis of antifolate resistance.
Anti-purines – Purines are chemical building blocks in the creation of the nucleotides that make up DNA and RNA. Anti-purines prevent the development of these nucleotides, which stops DNA production.
- 6-Mercaptopurine, approved in 1953 for leukemia and in 1989 for the treatment of metastatic melanoma.
- Dacarbazine was FDA approved in 1953 but it is still the most active agent within metastatic melanoma therapies.
- Fludarabine was approved in 1991 for adult leukemia.
Anti-pyrimidines – Pyrimidines are the other chemical building blocks in the creation of the nucleotides that make up DNA and RNA. Anti-pyrimidines prevent the development of these nucleotides, which stops DNA production.
- Cytosar-U (Arabinosylcytosine)was approved in 1991 for the treatment of leukemia.
- Gemzar (Gemcitabine) was approved for breast cancer in 2004 and ovarian cancer in 2006.
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