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Erivedge
Vismodegib (trade name Erivedge ) is a drug for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma . The drug was developed by the biotechnology/pharmaceutical company Genentech. Indication Vismodegib is indicated for patients with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation. Mechanism of action The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents t ...
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Genentech
Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within Roche. Historically, the company is regarded as the world's first biotechnology company. As of July 2021, Genentech employed 13,539 people. History The company was founded in 1976 by venture capitalist Robert A. Swanson and biochemist Herbert Boyer. Boyer is considered to be a pioneer in the field of recombinant DNA technology. In 1973, Boyer and his colleague Stanley Norman Cohen demonstrated that restriction enzymes could be used as "scissors" to cut DNA fragments of interest from one source, to be ligated into a similarly cut plasmid vector. While Cohen returned to the laboratory in academia, Swanson contacted Boyer to found the company. Boyer worked with Arthur Riggs and Keiichi Itakura from the Beckman Research Institute, and the ...
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Dysgeusia
Dysgeusia, also known as parageusia, is a distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is a decrease in taste sensitivity. An alteration in taste or smell may be a secondary process in various disease states, or it may be the primary symptom. The distortion in the sense of taste is the only symptom, and diagnosis is usually complicated since the sense of taste is tied together with other sensory systems. Common causes of dysgeusia include chemotherapy, asthma treatment with albuterol, and zinc deficiency. Liver disease, hypothyroidism, and rarely certain types of seizures can also lead to dysgeusia. Different drugs could also be responsible for altering taste and resulting in dysgeusia. Due to the variety of causes of dysgeusia, there are many possible treatments that are effective in alleviating or terminating the symptoms of dysgeusia. These include artificial saliva, pilocarpine, zin ...
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Smoothened
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA). Smoothened (Smo) is a key transmembrane protein that is a key component of the hedgehog signaling pathway, a cell-cell communication system critical for embryonic development and adult tissue homeostasis. Mutations in proteins that relay Hh signals between cells cause birth defects and cancer. The protein that carries the Hh signal across the membrane is the oncoprotein and G-protein coupled receptor (GPCR) Smoothened (Smo). Smo is regulated by a separate transmembrane receptor for Hh ligands called Patched (Ptc). Ptc itself is a tumor suppressor that keeps ...
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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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Chloroarenes
In organic chemistry, an aryl halide (also known as haloarene) is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications. Preparation The two main preparatory routes to aryl halides are direct halogenation and via diazonium salts. Direct halogenation In the Friedel-Crafts halogenation, Lewis acids serve as catalysts. Many metal chlorides are used, examples include iron(III) chloride or aluminium chloride. The most important aryl halide, chlorobenzene is produced by this route. Monochlorination of benzene is always accompanied by formation of the dichlorobenzene derivatives. Arenes with electron donating groups react with halogens even in the absence of ...
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Cyclopamine
Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily (''Veratrum californicum'') that causes fatal birth defects. It prevents the embryonic brain from separating into two lobes (an extreme form of holoprosencephaly), which in turn causes the development of a single eye (cyclopia). The chemical was named after this effect, as it was originally noted by Idaho lamb farmers who contacted the US Department of Agriculture after their herds gave birth to cycloptic lambs in 1957. It then took more than a decade to identify the corn lily as the culprit. Later work suggested that different rain patterns caused the sheep to graze differently, impacting the amount of corn lily ingested by pregnant sheep. The poison interrupts the sonic hedgehog signaling pathway during development, thus causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Departm ...
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Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ...
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Side Effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug. Developing drugs is a complicated process, because no two people are exactly the same, so even drugs that have virtually no side effects, might be difficult for some people. Also, it is difficult to make a drug that targets one part of the body but that does not affect other parts, the fact that increases the risk of side effects in the untargeted parts. Occasionally, drugs are prescribed or procedures performed specifically for their side effects; in that case, said side effect ceases to be a side effect and is now an intended effect. For instance, X-rays were historically (and are currently) used as an imaging technique; the discovery of their oncolytic capability led to their employ in radiotherapy (ablation o ...
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