Purine Analogue
Purine analogues are antimetabolites that mimic the structure of metabolic purines. Examples * Nucleobase analogues **Thiopurines such as thioguanine are used to treat acute leukemias and remissions in acute granulocytic leukemias. ***Azathioprine is the main immunosuppressive cytotoxic substance. A prodrug, it is widely used in transplantation to control rejection reactions. It is nonenzymatically cleaved to mercaptopurine, a purine analogue that inhibits DNA synthesis. By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both cell immunity and humoral immunity. It also successfully suppresses autoimmunity. ***Mercaptopurine *** Thioguanine *Nucleoside analogues **Clofarabine ** Pentostatin and cladribine are adenosine analogs that are used primarily to treat hairy cell leukemia. *Nucleotide analogues ** Fludarabine inhibits multiple DNA polymerases, DNA primase, and DNA ligase I, and is S phase-specific (since these enzyme ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Antimetabolite
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 in 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 Class ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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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. Approval Clolar was Food and Drug Administration (FDA) approved 28 December 2004. (Under accelerated approval regulations requiring further clinical studies.) Side effects * Tumor lysis syndrome (TLS). Clofarabine quickly kills leukaemia cells in the blood. The body may react to this. Signs include hyperkalemia, hyperuricemia, and hyperphosphatemia. TLS is very serious and can lead to death if it is not treated right aw ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Purine
Purine is a 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, and in various seafoods, high-fructose beverages, alcohol, and yeast products. Examples of high-purine food sources include anchovies, sardines, liver, beef, kidneys, brains, monkfish, dried mackerel, and shrimp. Foods particularly rich in hypoxanthine, adenine, and guanine lead to higher blood levels of uric acid. Foods having more than 200 mg of hypoxanthine per 100 g, particularly animal and fish meats containing hypoxanthine as more than 50% of total purines, are more likely to increase uri ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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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 ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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DNA Ligase I
DNA ligase 1 also DNA ligase I, is an enzyme that in humans is encoded by the ''LIG1'' gene. DNA ligase 1 is the only known eukaryotic DNA ligase involved in both DNA replication and repair, making it the most studied of the ligases. Discovery It was known that DNA replication occurred through a double strand break, but the enzyme responsible for ligating the strands back together, and mechanism of action, was unknown until Lehman, Gellert, Richardson, and Hurwitz laboratories, made significant contributions to the discovery of DNA ligase in 1967. Recruitment and regulation ''LIG1'' encodes a, 120kDa enzyme, 919 residues long, known as DNA ligase 1. The DNA ligase 1 polypeptide contains an N-terminal replication factory-targeting sequence (RFTS), followed by a nuclear localization sequence (NLS), and three functional domains. The three domains consist of an N-terminal DNA binding domain (DBD), and catalytic nucleotidyltransferase (NTase), and C-terminal oligonucleotide ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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DNA Primase
DNA primase is an enzyme involved in the replication of DNA and is a type of RNA polymerase. Primase catalyzes the synthesis of a short RNA (or DNA in some living organisms) segment called a primer complementary to a ssDNA (single-stranded DNA) template. After this elongation, the RNA piece is removed by a 5' to 3' exonuclease and refilled with DNA. Function In bacteria, primase binds to the DNA helicase forming a complex called the primosome. Primase is activated by the helicase where it then synthesizes a short RNA primer approximately 11 ±1 nucleotides long, to which new nucleotides can be added by DNA polymerase. Archaeal and eukaryote primases are heterodimeric proteins with one large regulatory and one minuscule catalytic subunit. The RNA segments are first synthesized by primase and then elongated by DNA polymerase. Then the DNA polymerase forms a protein complex with two primase subunits to form the alpha DNA Polymerase primase complex. Primase is one of the ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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DNA Polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalysis, catalyze the chemical reaction : deoxynucleoside triphosphate + DNAn pyrophosphate + DNAn+1. DNA polymerase adds nucleotides to the Directionality (molecular biology), three prime (3')-end of a DNA strand, one nucleotide at a time. Every time a Cell division, cell divides, DNA polymerases are required to duplicate the cell's DNA, so that a copy of the original DNA molecule can be passed to each daughter cell. In this way, genetic information is passed down from generation to generation. Before replication can take place, an enzy ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Fludarabine
Fludarabine is a purine analogue and antineoplastic agent. It is generally used as its 5-O-phosphorylated form known as fludarabine phosphate, sold under the brand name Fludara among others. It 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. Common side effects include nausea, diarrhea, fever, rash, shortness of breath, numbness, vision changes, and feeling tired. Severe side effects include brain dysfunction, low blood cell counts, and lung inflammation. Use in pregnancy will likely result in harm to the fetus. Fludarabine is in the purine analog family of medications and works by interfering with the duplication of DNA. Fludarabine was approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines. Medica ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hairy Cell Leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the prevalence is 3 cases per 100,000 in Europe with a lower prevalence in Asia, Africa and the Middle East. HCL has an indolent course but with frequent relapses, but with treatment life expectancy is usually the same as that for the general population. HCL was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the cytoplasmic projections from malignant B cells under a ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Cladribine
Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia (formally named leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis. Cladribine is a purine analogue that selectively targets and suppresses lymphocytes implicated in the underlying pathogenesis of multiple sclerosis and B-cell leukaemia. Chemically, it mimics the nucleoside deoxyadenosine. However, unlike deoxyadenosine, it is relatively resistant to breakdown by the enzyme adenosine deaminase, which causes it to accumulate in targeted cells and interfere with the cell's ability to process DNA. Cladribine is taken up by cells via transporter proteins. Once inside a cell, cladribine undergoes phosphorylation by the enzyme deoxycytidine kinase (DCK) to produce mononucleotide 2-chlorodeoxyadenosin ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Pentostatin
Pentostatin (or 2′-deoxycoformycin, trade name Nipent, manufactured by SuperGen) is an anticancer chemotherapeutic drug. Medical uses Pentostatin is used to treat hairy cell leukemia. It is given by intravenous infusion once every two weeks for three to six months. Additionally, pentostatin has been used to treat steroid-refractory acute and chronic graft-versus-host disease. Pentostatin is also used in chronic lymphocytic leukemia (CLL) patients who have relapsed. Mechanism of action It is classified as a purine analog, which is a type of antimetabolite. It mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, interfering with the cell's ability to process DNA. Cancer cells generally divide more often than healthy cells; DNA is highly involved in cell division (mitosis) and drugs which target DNA-related processes are therefore more toxic to cancer cells than healthy cells. Production Pentostatin was originally made by ''Streptomyces an ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Nucleoside Analogue
Nucleoside analogues are structural analogues of a nucleoside, which normally contain a nucleobase and a sugar. Nucleotide analogues are analogues of a nucleotide, which normally has one to three phosphates linked to a nucleoside. Both types of compounds can deviate from what they mimick in a number of ways, as changes can be made to any of the constituent parts (nucleobase, sugar, phosphate). They are related to nucleic acid analogues. Nucleoside and nucleotide analogues can be used in therapeutic drugs, including a range of antiviral products used to prevent viral replication in infected cells. The most commonly used is acyclovir. Nucleotide and nucleoside analogues can also be found naturally. Examples include ddhCTP (3ʹ-deoxy-3′,4ʹdidehydro-CTP) produced by the human antiviral protein viperin and sinefungin (a S-Adenosyl methionine analogue) produced by some '' Streptomyces''. Function These agents can be used against hepatitis B virus, hepatitis C virus, herpe ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |