Marimastat
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Marimastat
Marimastat was a proposed antineoplastic drug developed by British Biotech. It acted as a broad-spectrum matrix metalloproteinase inhibitor A matrix metalloproteinase inhibitor (MMPI) inhibits matrix metalloproteinases. As they inhibit cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic d .... Marimastat performed poorly in clinical trials, and development was terminated. This may be, however, a result of targeting cancer at too late of a stage. This is supported by the fact that MMP inhibitors have more recently been shown in animal models to be more effective in earlier stages of cancers. (Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284, 808-812. Bergers, G., Javaherian, K., Lo, K.-M., Folkman, J., and Hanahan, D. (1999)). See also * Batimastat References Experimental cancer drugs Hydroxamic acids Matrix metalloproteinase inhibito ...
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British Biotech
British Biotech was a British-based biotechnology company founded as British Biotechnology Limited in 1986 by former G D Searle managers Keith McCullagh and Brian Richards. It was the first British biotech company to be publicly listed when it was floated on 1 July 1992. Controversy In 1996, despite having no compounds on or near the market, the company was temporarily valued at nearly $2.5 billion, largely on the basis of its two main development drugs: ''marimastat'' (a novel matrix metalloprotease inhibitor for cancer treatment) and lexipafant (''Zacutex'', for pancreatitis). ''Batimastat'' (codename BB94) progressed as far as stage 3 in its clinical trial, although not orally bioavailable, there are other methods of administration, including transdermal. In February 1998, Dr Andrew Millar was dismissed as Head of Clinical Research and went on to make allegations that "the Board were running a business plan consistent only with extreme and unfounded optimism". These e ...
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Batimastat
Batimastat (mnemonic: ''batty''-mustard) (INN/USAN, codenamed BB-94) is a drug that was invented by Laurie Hines of British Biotech (now Vernalis). It is an antimetastatic drug that belongs to the family of drugs called angiogenesis inhibitors. It acts as a matrix metalloproteinase inhibitor (MMPI) by mimicking natural MMPI peptides. Dan Lednicer wrote about this compound in book #6 of his organic drug synthesis series. Batimastat was the first MMPI that went into clinical trials. First results of a Phase I trial appeared in 1994. The drug reached Phase III but was never marketed; mainly because it couldn't be administered orally (as opposed to the newer and chemically similar MMPI marimastat), and injection into the peritoneum caused peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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Matrix Metalloproteinase Inhibitor
A matrix metalloproteinase inhibitor (MMPI) inhibits matrix metalloproteinases. As they inhibit cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ... they have antiangiogenic effects. They may be both endogenous and exogenous. The most notorious ''endogenous'' metalloproteinases are tissue inhibitors of metalloproteinases (TIMPs). There are also cartilage-derived angiogenesis inhibitors. ''Exogenous'' matrix metalloproteinase inhibitors were developed as anticancer drugs. Examples include: * Batimastat * Cipemastat * Ilomastat * Marimastat * MMI270 * Prinomastat * Rebimastat * Ro 28-2653 * Tanomastat Metalloproteinase inhibitors are found in numerous marine organisms, including fish, cephalopods, mollusks, algae, and bacteria. See also * Drug discovery and ...
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National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship. NCI is the oldest and has the largest budget and research program of the 27 institutes and centers of the NIH ($6.9 billion in 2020). It fulfills the majority of its mission via an extramural program that provides grants for cancer research. Additionally, the National Cancer Institute has intramural research programs in Bethesda, Maryland, and at the Frederick National Laboratory for Cancer Research at Fort Detrick in Frederick, Maryland. The NCI receives more than in funding each ...
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Experimental Cancer Drugs
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies. A child may carry out basic experiments to understand how things fall to the ground, while teams of scientists may take years of systematic investigation to advance their understanding of a phenomenon. Experiments and other types of hands-on activities are very important to student learning in the science classroom. Experiments can raise test scores and help a student become more engaged and interested in the material they are learning, especially when used over time. Experiments can vary from personal and informal natural comparisons (e. ...
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Hydroxamic Acids
A hydroxamic acid is a class of organic compounds bearing the functional group RC(O)N(OH)R', with R and R' as organic residues and CO as a carbonyl group. They are amides (RC(O)NHR') wherein the NH center has an OH substitution. They are often used as metal chelators. Synthesis and reactions Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid, the overall equation is: :C6H5CO2Me + NH2OH → C6H5C(O)NHOH + MeOH Hydroxamic acids can also be synthesized from aldehydes and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. A well-known reaction of hydroxamic acid esters is the Lossen rearrangement. Coordination chemistry and biochemistry File:Ferrichrome.svg, Ferrichrome File:Deferoxamine-2D-skeletal.png , Deferoxamine File:Rhodotorulic acid.svg, Rhodotorulic acid File:Fe(hydroxamate)3.svg, Fe(III) complex of triacetylfusarinine Many hydroxamates have been ...
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