Purine analogue

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Purine analogues are antimetabolites that mimic the structure of metabolic purines.

Contents

Examples

Medical uses

Purine antimetabolites are commonly used to treat cancer by interfering with DNA replication. [1]

Related Research Articles

Leukemia Group of blood cancers that usually begin in the bone marrow

Leukemia, also spelled leukaemia, is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, feeling tired, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.

Immunosuppressive drug

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications are drugs that inhibit or prevent activity of the immune system.

Methotrexate A medicine

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, ectopic pregnancy, and for medical abortions. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

Azathioprine

Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, and in kidney transplants to prevent rejection. It is taken by mouth or injected into a vein.

Cytarabine Chemical compound (chemotherapy medication)

Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by injection into a vein, under the skin, or into the cerebrospinal fluid. There is a liposomal formulation for which there is tentative evidence of better outcomes in lymphoma involving the meninges.

A nucleoside triphosphate is a molecule containing a nitrogenous base bound to a 5-carbon sugar, with three phosphate groups bound to the sugar. It is an example of a nucleotide. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways.

Mercaptopurine

Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), Crohn's disease, and ulcerative colitis. For acute lymphocytic leukemia it is generally used with methotrexate. It is taken by mouth.

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.

History of cancer chemotherapy

The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.

Clofarabine

Clofarabine is a purine nucleoside antimetabolite marketed in the United States and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children after at least two other types of treatment have failed. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out. Ongoing trials are assessing its efficacy for managing other cancers.

Nucleoside analogue

Nucleoside analogues are nucleosides which contain a nucleic acid analogue and a sugar. Nucleotide analogs are nucleotides which contain a nucleic acid analogue, a sugar, and a phosphate groups with one to three phosphates.

Fludarabine

Fludarabine, sold under the brand name Fludara among others, is a chemotherapy medication used in the treatment of leukemia and lymphoma. These include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, acute myeloid leukemia, and acute lymphocytic leukemia. It is given by injection into a vein or by mouth.

Pentostatin

Pentostatin is an anticancer chemotherapeutic drug.

Tioguanine

Tioguanine, also known as thioguanine or 6-thioguanine (6-TG) is a medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and chronic myeloid leukemia (CML). Long-term use is not recommended. It is given by mouth.

Decitabine

Decitabine, or 5-aza-2'-deoxycytidine, acts as a nucleic acid synthesis inhibitor. It is a drug for the treatment of myelodysplastic syndromes, a class of conditions where certain blood cells are dysfunctional, and for acute myeloid leukemia (AML). Chemically, it is a cytidine analog.

Pyrimidine analogues are antimetabolites which mimic the structure of metabolic pyrimidines.

VAMP regimen or VAMP chemotherapy is a four-drug combination chemotherapy regimen, used today in the treatment of Hodgkin lymphoma. It was one of the earliest combination chemotherapy regimens, originally developed as a treatment for childhood leukemia by a group of researchers at the National Cancer Institute led by Emil Frei and Emil Freireich. The first clinical trial of VAMP began in 1961. Because it was the first time that four chemotherapeutic agents were used at once, the trial was highly controversial at its time. Although new combination chemotherapy regimens have replaced the use of VAMP in the treatment of childhood leukemia, VAMP is considered an important precursor to modern treatments, confirming the effectiveness of combination chemotherapy and leading to the use of combination chemotherapy regimens to treat other types of cancer.

"7+3" in the context of chemotherapy is an acronym for a chemotherapy regimen that is most often used today as first-line induction therapy in acute myelogenous leukemia, excluding the acute promyelocytic leukemia form, which is better treated with ATRA and/or arsenic trioxide and requires less chemotherapy.

FLAG is an acronym for a chemotherapy regimen used for relapsed and refractory acute myeloid leukemia (AML). The standard FLAG regimen consists of:

  1. Fludarabine: an antimetabolite that is not active toward AML, but increases formation of an active cytarabine metabolite, ara-CTP, in AML cells;
  2. High-dose cytarabine : an antimetabolite that has been proven to be the most active toward AML among various cytotoxic drugs in single-drug trials;
  3. Granulocyte colony-stimulating factor (G-CSF): a glycoprotein that shortens the duration and severity of neutropenia.

ADE is a chemotherapy regimen most often used as an induction or consolidation regimen in acute myelogenous leukemia, especially in poor-risk patients or those refractory to the standard first-line induction with standard "7+3" regimen or who are relapsed after the standard chemotherapy.

References

  1. Parker, William B. (2009). "Enzymology of Purine and Pyrimidine Antimetabolites Used in the Treatment of Cancer". Chem Rev. 109 (7): 2880–2893. doi:10.1021/cr900028p. PMC   2827868 . PMID   19476376.