Antimetabolic Agent
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Antimetabolic Agent
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. Function Cancer treatment Antimetabolites can be used in cancer treatment, as they interfere with DNA production and therefore cell division and tumor growth. Because cancer cells spend more time dividing than other cells, inhibiting cell division harms tumor cells more than other cells. Antimetabolite drugs are commonly used to treat leukemia, cancers of the breast, ovary, and the gastrointestinal tract, as well as other types of cancers. In the Anatomical Therapeutic Chemical Classif ...
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Methotrexate And Folic Acid Compared
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. 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. Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It acts by blocking the body's use of folic acid. Methotrexate was first made in 1947 and i ...
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Floxuridine
Floxuridine (also ''5-fluorodeoxyuridine'') is an oncology drug that belongs to the class known as antimetabolites. Specifically, floxuridine is a pyrimidine analog, classified as a deoxyuridine. The drug is usually administered via an artery, and most often used in the treatment of colorectal cancer. The quality of life and survival rates of individuals that receive continuous hepatic artery infusion of floxuridine for colorectal cancer metastases is significantly higher than control groups. Floxuridine can also be prescribed for the treatment of kidney and stomach cancers. In vitro uses of floxuridine include 5-minute treatments of fluorouracil, floxuridine, and mitomycin to increase cell proliferation in Tenon's capsule fibroblasts. Biosynthesis Immobilized ''Aeromonas salmonicida'' ATCC 27013, when exposed to thymidine and 5-fluorouracil in phosphate buffer at room temperature for one hour, can synthesize floxuridine and thymine. Pharmacology Floxuridine primarily works by ...
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Thymidine
Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. In cell biology it is used to synchronize the cells in G1/early S phase. The prefix deoxy- is often left out since there are no precursors of thymine nucleotides involved in RNA synthesis. Before the boom in thymidine use caused by the need for thymidine in the production of the antiretroviral drug azidothymidine (AZT), much of the world's thymidine production came from herring sperm. Thymidine occurs almost exclusively in DNA but it also occurs in the T-loop of tRNA. Structure and properties In its composition, deoxythymidine is a nucleoside composed of deoxyribose (a pentose sugar) joined to the pyrimidine base thymine. Deoxythymidine can be phosphorylated with one, two or three phosphoric acid groups, creating dTMP (deoxythymidine ...
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Cell Cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei ( eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis). During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the mitotic phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps ...
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S Phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved. Regulation Entry into S-phase is controlled by the G1 restriction point (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable. Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3 cyclin, which complexes with the cyclin dependent kinase CDK2. The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating ...
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Pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions). In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U). Occurrence and history The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, when Grimaux reported the ...
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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), acute promyelocytic leukemia (APL), Crohn's disease, and ulcerative colitis. For acute lymphocytic leukemia it is generally used with methotrexate. It is taken by mouth. Common side effects include bone marrow suppression, liver toxicity, vomiting, and loss of appetite. Other serious side effects include an increased risk of future cancer and pancreatitis. Those with a genetic deficiency in thiopurine S-methyltransferase are at higher risk of side effects. Use in pregnancy may harm the baby. Mercaptopurine is in the thiopurine and antimetabolite family of medications. Mercaptopurine was approved for medical use in the United States in 1953. It is on the World Health Organization's List of Essential Medicines. Medical uses It is used to treat acute lymphocytic leukemia, Crohn's d ...
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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 listed by the International Agency for Research on Cancer as a group 1 carcinogen (carcinogenic to humans). It is taken by mouth or injected into a vein. Common side effects include bone-marrow suppression and vomiting. Bone-marrow suppression is especially common in people with a genetic deficiency of the enzyme thiopurine S-methyltransferase. Other serious risk factors include an increased risk of certain cancers. Use during pregnancy may result in harm to the baby. Azathioprine is in the purine analogue and antimetabolite family of medications. It works via 6-thioguanine to disrupt the making of RNA and DNA by cells. Azathioprine was first made in 1957. It is on the World Hea ...
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Purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature. Dietary sources Purines are found in high concentration in meat and meat products, especially internal organs such as liver and kidney. In general, plant-based diets are low in purines. High-purine plants and algae include some legumes (lentils and Black-eyed pea, black eye peas) and Spirulina (dietary supplement), spirulina. Examples of high-purine sources include: sweetbreads, Anchovies as food, anchovies, Sardines as food, sardines, liver, beef kidneys, Brain as food, brains, meat extracts (e.g., Oxo (food), Oxo, Bovril), herring, mackerel, scallops, game meats, yeast (beer, yeast extract, nutritional yeast) and g ...
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Phototrexate
Phototrexate is a photochromic antifolate drug developed at the Institute for Bioengineering of Catalonia (IBEC, The Barcelona Institute of Science and Technology). In particular, it is a photopharmacological agent that behaves as light-regulated inhibitor of the dihydrofolate reductase (DHFR) enzyme. Phototrexate is a photoisomerizable structural analogue of the chemotherapy agent methotrexate. It is also an example of "azologization". Pharmacological effects of phototrexate can be switched on and off by UVA and visible light, respectively. Phototrexate is almost inactive in its ''trans'' configuration while it behaves as a potent antifolate in its ''cis'' configuration. It can also spontaneously self-deactivate in the dark. See also * Cancer * Psoriasis * Psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire f ...
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Pemetrexed
Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC).. It is available as a generic medication. Medical use In February 2004, the U.S. Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the mesothelium, the thin layer of tissue that covers many of the internal organs, in combination with cisplatin for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology. Carboplatin Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer. However, the rela ...
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Methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. 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. Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It acts by blocking the body's use of folic acid. Methotrexate was first made in 1947 and ...
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