Ribonucleotide Reductase Inhibitor
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Ribonucleotide Reductase Inhibitor
Ribonucleotide reductase inhibitors are a family of anti-cancer drugs that interfere with the growth of tumor cells by blocking the formation of deoxyribonucleotides (building blocks of DNA). Examples include: * motexafin gadolinium. * hydroxyurea * fludarabine, cladribine, gemcitabine, tezacitabine, and triapine * gallium maltolate, gallium nitrate See also * Ribonucleotide reductase Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of th ... References External links Ribonucleotide reductase inhibitorentry in the public domain NCI Dictionary of Cancer Terms Antineoplastic drugs Oxidoreductase inhibitors {{Antineoplastic-drug-stub ...
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Anti-cancer Drug
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targe ...
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Tumor Cells
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially m ...
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Deoxyribonucleotides
A deoxyribonucleotide is a nucleotide that contains deoxyribose. They are the monomeric units of the informational biopolymer, deoxyribonucleic acid ( DNA). Each deoxyribonucleotide comprises three parts: a deoxyribose sugar ( monosaccharide), a nitrogenous base, and one phosphoryl group. The nitrogenous bases are either purines or pyrimidines, heterocycles whose structures support the specific base-pairing interactions that allow nucleic acids to carry information. The base is always bonded to the 1'-carbon of the deoxyribose, an analog of ribose in which the hydroxyl group of the 2'-carbon is replaced with a hydrogen atom. The third component, the phosphoryl group, attaches to the deoxyribose monomer via the hydroxyl group on the 5'-carbon of the sugar. When deoxyribonucleotides polymerize to form DNA, the phosphate group from one nucleotide will bond to the 3' carbon on another nucleotide, forming a phosphodiester bond via dehydration synthesis. New nucleotides are always add ...
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Motexafin Gadolinium
Motexafin gadolinium (proposed tradename Xcytrin) is an inhibitor of thioredoxin reductase and ribonucleotide reductase Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of th .... It has been proposed as a possible chemotherapeutic agent in the treatment of brain metastases. History On May 9, 2006, a New Drug Application was submitted to the United States Food and Drug Administration (FDA) by Pharmacyclics, Inc. In December 2007, the FDA issued a not approvable letter for motexafin gadolinium. References Organogadolinium compounds {{biochemistry-stub ...
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Hydroxyurea
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and decreases the number of attacks. It is taken by mouth. Common side effects include bone marrow suppression, fevers, loss of appetite, psychiatric problems, shortness of breath, and headaches. There is also concern that it increases the risk of later cancers. Use during pregnancy is typically harmful to the baby. Hydroxycarbamide is in the antineoplastic family of medications. It is believed to work by blocking the making of DNA. Hydroxycarbamide was approved for medical use in the United States in 1967. It is on the World Health Organization's List of Essential Medicines. Hydroxycarbamide is available as a generic medication. Medical uses Hydroxycarbamide is used for the following indications: * Myeloproliferative disease (primar ...
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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. Medical us ...
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Cladribine
Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is indicated for the treatment of adult patients with highly active forms of relapsing-remitting multiple sclerosis. Cladribine (2-chloro-2'-deoxyadenosine -CdA 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 adenosine. However, unlike adenosine, 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 ...
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Gemcitabine
Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by intravenous infusion. It acts against neoplastic growth, and it inhibits the replication of Orthohepevirus A, the causative agent of Hepatitis E, through upregulation of interferon signaling. Common side effects include bone marrow suppression, liver and kidney problems, nausea, fever, rash, shortness of breath, mouth sores, diarrhea, neuropathy, and hair loss. Use during pregnancy will likely result in fetal harm. Gemcitabine is in the nucleoside analog family of medication. It works by blocking the creation of new DNA, which results in cell death. Gemcitabine was patented in 1983 and was approved for medical use in 1995. Generic versions were introduced in Europe in 2009 and in the US in 2010. It is on the WHO Model List of Essentia ...
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Tezacitabine
Tezacitabine is a ribonucleotide reductase inhibitor. It is a synthetic purine nucleoside analogue with potential antineoplastic activity. It is used in synthetic DNA In September 2021, Synthetic Genomics Inc. (SGI), a private company located in La Jolla, California, changed its name to Viridos. The company is focused on the field of synthetic biology, especially harnessing photosynthesis with micro algae to .... References Nucleosides Organofluorides Pyrimidones {{organic-compound-stub ...
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Triapine
3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, also called Triapine) is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called ribonucleotide reductase inhibitors. 3AP is a potent inhibitor of ribonucleotide reductase, the rate determining enzyme in the supply of deoxynucleotides (DNA building blocks) for DNA synthesis. DNA synthesis is required for cellular proliferation and DNA repair. It is a very strong iron chelator and in the body it is likely that the iron chelate is the active species that quenches the active site tyrosyl radical required by ribonucleotide reductase for its enzymatic activity. The 3AP iron chelate is redox active and there have been several reports in the literature ascribing this property to some of the biological activities of 3AP. 3AP was chosen, based on the results of studying and the screening these products, as the candidate inhibitor most likely to express activity in the setting of human ...
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Gallium Maltolate
Gallium maltolate is a coordination complex consisting of a trivalent gallium cation coordinated to three maltolate ligands. The compound is a potential therapeutic agent for cancer, infectious disease, and inflammatory disease. A cosmetic skin cream containing gallium maltolate is marketed under the name Gallixa. It is a colorless solid with significant solubility in both water and lipids ( octanol-water partition coefficient = 0.41). Mechanism of action Gallium maltolate delivers gallium with higher oral bioavailability than that of gallium salts such as gallium nitrate and gallium trichloride. ''In vitro'' studies have found gallium to be antiproliferative due primarily to its ability to mimic ferric iron (Fe3+). Ferric iron is essential for DNA synthesis, as it is present in the active site of the enzyme ribonucleotide reductase, which catalyzes the conversion of ribonucleotides to the deoxyribonucleotides required for DNA. Gallium is taken up by the rapidly proliferati ...
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Gallium Nitrate
Gallium nitrate (brand name Ganite) is the gallium salt of nitric acid with the chemical formula Ga(NO3)3. It is a drug used to treat symptomatic hypercalcemia secondary to cancer. It works by preventing the breakdown of bone through the inhibition of osteoclast activity, thus lowering the amount of free calcium in the blood.Gallium Nitrate monograph. Lexi-Comp Online, Lexi-Drugs Online, Lexi-Comp Inc. Hudson, OH. Available at. Accessed September 13th, 2008. Gallium nitrate is also used to synthesize other gallium compounds. History Gallium (Ga) was discovered in 1875 by P.É. Lecoq de Boisbaudran. In most of its compounds, gallium is found with an oxidation number of 3+. Gallium chemically behaves similarly to iron 3+ when forming a coordination complex. That means gallium(III) and iron(III) are similar in similar coordination number, electrical charge, ion diameter and electron configuration. Biological activity Gallium atoms are bound to the phosphates of DNA at low galli ...
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