Zebularine
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Zebularine
Zebularine is a nucleoside analog of cytidine. It is a transition state analog inhibitor of cytidine deaminase by binding to the active size as covalent hydrates. Also shown to inhibit DNA methylation and tumor growth both in vitro and in vivo. In a small study of mice with a defective ''Adenomatous polyposis coli'' gene, oral administration of zebularine to males had no effect on the overall methylation of DNA or the number of polyps, but in females the average number of polyps was reduced from 58 to 1. It has therefore been suggested for drug use as a prototype of epigenetic therapy for cancer chemoprevention Chemoprevention (also chemoprophylaxis) refers to the administration of a medication for the purpose of preventing disease or infection. Antibiotics, for example, may be administered to patients with disorders of immune system function to prevent b .... References {{reflist Nucleosides Pyrimidones ...
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Epigenetic Therapy
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly. Background Epigenetics refers to the study of changes in gene expressions that do not result from alterations in the DNA sequence'. Altered gene expression patterns can result from chemical modifications in DNA and chromatin, to changes in several regulatory mechanisms. Epigenetic markings can be inherited in some cases, and can change in response to environmental stimuli over the course of an organism's life. Many diseases are known to have a genetic component, but the epigenetic mechanisms underlying many conditions are still being discovered. A significant number of diseases are known to change the expression of genes within the body, and epigenetic involvement is a ...
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Nucleoside Analog
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 group with one to three phosphates. 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, although its inclusion in this category is uncertain, because it acts as a nucleoside but contains no actual sugar, as the sugar ring is replaced by an open-chain structure. 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, herpes simplex, and HIV. Once they are phosphorylate ...
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Cytidine
Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as a ribofuranose) via a β-N1- glycosidic bond. Cytidine is a component of RNA. It is a white water-soluble solid. which is only slightly soluble in ethanol. Dietary sources Dietary sources of cytidine include foods with high RNA (ribonucleic acid) content, such as organ meats, brewer's yeast, as well as pyrimidine-rich foods such as beer. During digestion, RNA-rich foods are broken-down into ribosyl pyrimidines (cytidine and uridine), which are absorbed intact. In humans, dietary cytidine is converted into uridine, which is probably the compound behind cytidine's metabolic effects. Cytidine analogues A variety of cytidine analogues are known, some with potentially useful pharmacology. For example, KP-1461 is an anti-HIV agent that works as a viral mutagen, and zebularine exists in '' E. coli'' and is being examined for chemotherapy. Low doses of azacit ...
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Transition State Analog
Transition state analogs (transition state analogues), are chemical compounds with a chemical structure that resembles the transition state of a enzyme substrate, substrate molecule in an enzyme catalysis, enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by means of strain or distortions, moving the substrate towards the transition state. Transition state analogs can be used as inhibitors in enzyme-catalyzed reactions by blocking the active site of the enzyme. Theory suggests that enzyme inhibitors which resembled the transition state structure would bind more tightly to the enzyme than the actual substrate. Examples of drugs that are transition state analog inhibitors include flu medications such as the neuraminidase inhibitor oseltamivir and the HIV protease inhibitors saquinavir in the treatment of AIDS. Transition state analogue The transition state of a structure can best be described in regards to statistical mechanics where the energies of bonds break ...
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Cytidine Deaminase
Cytidine deaminase is an enzyme that in humans is encoded by the ''CDA'' gene. This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. It is one of several deaminases responsible for maintaining the cellular pyrimidine pool. Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias. Most cytidine deaminases act on RNA, and the few that act on DNA require ssDNA. A related activation-induced (cytidine) deaminase (AID) regulates antibody diversification, especially the process of somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major co ...
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DNA Methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. As of 2016, two nucleobases have been found on which natural, enzymatic DNA methylation takes place: adenine and cytosine. The modified bases are N6-methyladenineD. B. Dunn, J. D. Smith: ''The occurrence of 6-methylaminopurine in deoxyribonucleic acids.'' In: ''Biochem J.'' 68(4), Apr 1958, S. 627–636. PMID 13522672. ., 5-methylcytosineB. F. Vanyushin, S. G. Tkacheva, A. N. Belozersky: ''Rare bases in animal DNA.'' In: ''Nature.'' 225, 1970, S. 948–949. PMID 4391887. and N4- ...
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PubChem
PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information (NCBI), a component of the National Library of Medicine, which is part of the United States National Institutes of Health (NIH). PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be freely downloaded via FTP. PubChem contains multiple substance descriptions and small molecules with fewer than 100 atoms and 1,000 bonds. More than 80 database vendors contribute to the growing PubChem database. History PubChem was released in 2004 as a component of the Molecular Libraries Program (MLP) of the NIH. As of November 2015, PubChem contains more than 150 million depositor-provided substance descriptions, 60 million unique chemical structures, and 225 million biological activity test results (from over 1 million assay experiments performed on more t ...
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National Center For Biotechnology Information
The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is located in Bethesda, Maryland, and was founded in 1988 through legislation sponsored by US Congressman Claude Pepper. The NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. Major databases include GenBank for DNA sequences and PubMed, a bibliographic database for biomedical literature. Other databases include the NCBI Epigenomics database. All these databases are available online through the Entrez search engine. NCBI was directed by David Lipman, one of the original authors of the BLAST sequence alignment program and a widely respected figure in bioinformatics. GenBank NCBI had responsibility for making available the GenBank DNA seque ...
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Adenomatous Polyposis Coli
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the ''APC'' gene may result in colorectal cancer. ''APC'' is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the ''APC'' gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumor. The APC protein helps control how often a cell divides, how it attaches to other cells within a tissue, how the cell polarizes and the morphogenesis of the 3D structures, or whether a cell moves within or away from tissue. This protein also helps ensure that the chromosome number in cells produced through cell division is correct. The APC pro ...
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Cancer Prev Res
''Cancer Prevention Research'' is a peer-reviewed medical journal that publishes original studies, reviews, and commentaries in the fields of cancer prevention and interception. It was launched in 2008 by its publisher, the American Association for Cancer Research. The journal's current editors-in-chief An editor-in-chief (EIC), also known as lead editor or chief editor, is a publication's editorial leader who has final responsibility for its operations and policies. The highest-ranking editor of a publication may also be titled editor, managing ... are Raymond N. DuBois and Michael N. Pollak, who were appointed in 2018. References External links *{{Official website, http://cancerpreventionresearch.aacrjournals.org/ American Association for Cancer Research academic journals Oncology journals Publications established in 2008 Semi-monthly journals English-language journals ...
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Chemoprevention
Chemoprevention (also chemoprophylaxis) refers to the administration of a medication for the purpose of preventing disease or infection. Antibiotics, for example, may be administered to patients with disorders of immune system function to prevent bacterial infections (particularly opportunistic infection). Antibiotics may also be administered to healthy individuals to limit the spread of an epidemic, or to patients who have repeated infections (such as urinary tract infections) to prevent recurrence. It may also refer to the administration of heparin to prevent deep venous thrombosis in hospitalized patients. In some cases, chemoprophylaxis is initiated to prevent the spread of an existing infection in an individual to a new organ system, as when intrathecal chemotherapy is administered in patients with malignancy to prevent further infection. The use of chemoprophylaxis is limited primarily by two factors: risk and financial costs. * All medications have the potential to cause sid ...
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Nucleosides
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building-blocks of DNA and RNA. List of nucleosides and corresponding nucleobases The reason for 2 symbols, shorter and longer, is that the shorter ones are better for contexts where explicit disambiguation is superfluous (because context disambiguates) and the longer ones are for contexts where explicit disambiguation is judged to be needed or wise. For example, when discussing long nucleobase sequences in genomes, the CATG symbol system is much preferable to the Cyt-Ade-Thy-Gua symbol system (see '' N ...
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