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Salinosporamide A
Salinosporamide A (Marizomib) is a potent proteasome inhibitor being studied as a potential anticancer agent. It entered phase I human clinical trials for the treatment of multiple myeloma, only three years after its discovery in 2003. This marine natural product is produced by the obligate marine bacteria ''Salinispora tropica'' and ''Salinispora arenicola'', which are found in ocean sediment. Salinosporamide A belongs to a family of compounds, known collectively as salinosporamides, which possess a densely functionalized γ-lactam-β-lactone bicyclic core. History Salinosporamide A was discovered by William Fenical and Paul Jensen from Scripps Institution of Oceanography in La Jolla, CA. In preliminary screening, a high percentage of the organic extracts of cultured ''Salinispora'' strains possessed antibiotic and anticancer activities, which suggests that these bacteria are an excellent resource for drug discovery. ''Salinispora'' strain CNB-392 was isolated from a heat-tr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteasome Inhibitor
Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma. Mechanism Multiple mechanisms are likely to be involved, but proteasome inhibition may prevent degradation of pro-apoptotic factors such as the p53 protein, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. For example, bortezomib causes a rapid and dramatic change in the levels of intracellular peptides. Examples * The first non-peptidic proteasome inhibitor discovered was the natural product lactacystin. * Disulfiram has been proposed as another proteasome inhibitor. * Epigallocatechin-3-gallate has also been proposed. * Marizomib (salinosporamide A) has started clinical trials for multiple myeloma. * Oprozomib (ONX-0912), delanzomib (CEP-18770) have also started clinical trials. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MDA-MB-435
The NCI-60 cancer cell line panel is a group of 60 human cancer cell lines used by the National Cancer Institute (NCI) for the screening of compounds to detect potential anticancer activity. Purpose The screening procedure is called the NCI-60 Human Tumor Cell Lines Screen, and it is one of the Discovery & Development Services of NCI's Developmental Therapeutics Program (DTP). The screening rates for each cell line the cytostatic and cytotoxic impact of tested substances. Due to the diversity of the cell lines, it is possible to compare tested compounds by their effect patterns, high correlation potentially corresponding to similar effect mechanisms. An automated comparison against a database of more than 88,000 pure compounds and more than 34,000 crude extracts () is provided by the COMPARE tool, which shows a list of substances ranked by the Pearson correlation coefficients for a given test substance. The same panel is used in the Molecular Target Program for the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bortezomib
Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection. Common side effects include nausea, diarrhea, tiredness, low platelets, fever, numbness, low white blood cells, shortness of breath, rash and abdominal pain. Other severe side effects include low blood pressure, tumour lysis syndrome, heart failure, and reversible posterior leukoencephalopathy syndrome. It is in the class of medications known as proteasome inhibitor. It works by inhibiting proteasomes, cellular complexes that break down proteins. Bortezomib was approved for medical use in the United States in 2003 and in the European Union in 2004. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Medic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EC50
] Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. More simply, EC50 can be defined as the ''concentration required to obtain a 50% ..effect'' and may be also written as sub>50. It is commonly used as a measure of a drug's potency, although the use of EC50 is preferred over that of 'potency', which has been criticised for its vagueness. EC50 is a measure of concentration, expressed in molar units (M), where 1 M is equivalent to 1 mol/ L. The EC50 of a ''graded'' dose response curve therefore represents the concentration of a compound where 50% of its maximal effect is observed. The EC50 of a ''quantal'' dose response curve represents the concentration of a compound where 50% of the population exhibit a response, after a specified exposure duration. For clarification, a grade ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
In Vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from ''in vitro'' experiments may not fully or accurately predict the effects on a whole organism. In contrast to ''in vitro'' experiments, ''in vivo'' studies are those conducted in living organisms, including humans, and whole plants. Definition ''In vitro'' ( la, in glass; often not italicized in English usage) studies are conducted using components of an organism that have been isolated fro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Polyketide Synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity. History Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by heating dehy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is known as group 17. The word "halogen" means "salt former" (or "salt maker"). When halogens react with metals, they produce a wide range of salts, including calcium fluoride, sodium chloride (common table salt), silver bromide and potassium iodide. The group of halogens is the only periodic table group that contains elements in three of the main states of matter at standard temperature and pressure. All of the halogens form acids when bonded to hydrogen. Most halogens are typically produced from minerals or salts. The middle halogens—chlorine, bromine, and iodine—are often used as disinfectants. Organobromides are the most important class of flame retardants, while elemental halogens are dangerous and can be toxic. History The fl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetate
An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" also describes the conjugate acid, conjugate base or ion (specifically, the negatively charged ion called an anion) typically found in aqueous solution and written with the chemical formula . The neutral molecules formed by the combination of the acetate ion and a ''positive'' ion (called a cation) are also commonly called "acetates" (hence, ''acetate of lead'', ''acetate of aluminum'', etc.). The simplest of these is hydrogen acetate (called acetic acid) with corresponding salts, esters, and the polyatomic ion, polyatomic anion , or . Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In nature, acetate is the most common ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbon 13
Carbon-13 (13C) is a natural, stable isotope of carbon with a nucleus containing six protons and seven neutrons. As one of the environmental isotopes, it makes up about 1.1% of all natural carbon on Earth. Detection by mass spectrometry A mass spectrum of an organic compound will usually contain a small peak of one mass unit greater than the apparent molecular ion peak (M) of the whole molecule. This is known as the M+1 peak and comes from the few molecules that contain a 13C atom in place of a 12C. A molecule containing one carbon atom will be expected to have an M+1 peak of approximately 1.1% of the size of the M peak, as 1.1% of the molecules will have a 13C rather than a 12C. Similarly, a molecule containing two carbon atoms will be expected to have an M+1 peak of approximately 2.2% of the size of the M peak, as there is double the previous likelihood that any molecule will contain a 13C atom. In the above, the mathematics and chemistry have been simplified, however it can ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Salinosporamide A Biosynthesis
The salinosporamides are a group of closely related chemical compounds isolated from marine bacteria in the genus ''Salinispora''. They possess a densely functionalized γ-lactam-β-lactone bicyclic core. Salinosporamide A has attracted interest for its potential use in treating various types of cancer. In addition, a variety of synthetic analogs have been prepared. Chemical structures File:Salinosporamide A.svg, Salinosporamide A Salinosporamide A (Marizomib) is a potent proteasome inhibitor being studied as a potential anticancer agent. It entered phase I human clinical trials for the treatment of multiple myeloma, only three years after its discovery in 2003. This marin ... File:Salinosporamide B.svg, Salinosporamide B File:Salinosporamide C.svg, Salinosporamide C File:Salinosporamide D.svg, Salinosporamide D File:Salinosporamide E.svg, Salinosporamide E File:Salinosporamide F.svg, Salinosporamide F File:Salinosporamide G.svg, Salinosporamide G File:Salinosporamide H.svg, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Biosynthesis Of Nonproteinogenic Amino Acid
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism. The prerequisite elements for biosynthesis include: precursor compounds, chemical energy (e.g. ATP), and catalytic enzymes which may require coenzymes (e.g.NADH, NADPH). These elements create monomers, the building blocks for macromolecules. Some important biological macromolecules include: proteins, which are composed of amino acid monomers joined via peptide bonds, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
