Thapsigargin
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Thapsigargin
Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Structurally, thapsigargin is classified as a guaianolide, and is extracted from a plant, ''Thapsia garganica''. It is a tumor promoter in mammalian cells. Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. Store-depletion can secondarily activate plasma membrane calcium channels, allowing an influx of calcium into the cytosol. Depletion of ER calcium stores leads to ER stress and activation of the unfolded protein response. Non-resolved ER stress can cumulatively lead to cell death. Prolonged store depletion can protect against ferroptosis via remodeling of ER-synthesized phospholipids. Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR. Thapsigargin is useful in experimentation examining the impacts of incre ...
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Thapsia Garganica
''Thapsia'', commonly known as the deadly carrots, is a small genus of poisonous plants in the family Apiaceae. Their center of diversity is around the western Mediterranean, extending into the Atlantic coasts of Portugal and Morocco. Some species are used in traditional medicine. Description Species of ''Thapsia'' are herbaceous perennials, growing 50 to 200 cm high. The inflorescences are large, regularly distributed umbels. The seeds have four wings, and are the main characteristic of the genus, which is distributed in the Mediterranean, on the Iberian peninsula, and North Africa. The generic name ''Thapsia'' is derived from the Ancient Greek name θαψία (''thapsía'') for the members of the genus. The Greeks believe it to have originated from ancient Thapsos in Sicily. It has a long history of being used in ancient traditional medicine. Algerians used it as a pain-reliever though they recognized that the plant was deadly to camels. The Greek colony of Cyrene ...
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Germacrene B Synthase
Germacrenes are a class of volatile organic hydrocarbons, specifically, sesquiterpenes. Germacrenes are typically produced in a number of plant species for their antimicrobial and insecticidal properties, though they also play a role as insect pheromones. Two prominent molecules are germacrene A and germacrene D. Structures Germacrene has five isomers. Natural occurrences The essential oils of red deadnettle (''Lamium purpureum'') and hedgenettles (genus ''Stachys'') are characterized by their high contents of germacrene D, as is ''Clausena anisata :''Should not be confused with syzygium anisatum, a tree native to eastern Australian rainforests, used as a culinary herb.'' ''Clausena anisata'' (Willd.) Hook.f. ex Benth. is a deciduous shrub or small tree, belonging to the Rutaceae or Citr ...''. It is also a major component of patchouli oil. References Further reading General * Germacrene A * * * * * * Germacrene D ...
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Phil Baran
Phil S. Baran (born August 10, 1977) is a Professor in the Department of Chemistry at the Scripps Research Institute and Member of the Skaggs Institute for Chemical Biology.The Baran Laboratory
Scripps Research Institute
Baran has authored over 130 published scientific articles. He has several patents. His work is focused on synthesizing complex organic compounds, the development of new reactions, and the development of new reagents.


Early life and education

He received his BS in chemistry from in 1997 and his PhD from The Scripps Research Institute in 2001, under the supervision o ...
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Steven V
Stephen V may refer to: *Pope Stephen IV, aka Stephen V, Pope from 816 to 817 *Pope Stephen V (885–891) *Stephen V of Hungary (born before 1239 – 1272), King of Hungary and Croatia, Duke of Styria *Stephen V Báthory Stephen Báthory of Ecsed ( hu, Báthory István, ; ro, Ștefan Báthory; 1430–1493) was a Hungarian commander, 'dapiferorum regalium magister' (1458–?), judge royal (1471–1493) and voivode of Transylvania (1479–1493). ... (1430–1493), Hungarian commander, judge of the Royal Court and Prince of Transylvania * Stephen V of Moldavia (r. 1538–1540) {{hndis, Stephen 05 ...
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Total Synthesis
Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes it from semisynthesis. Syntheses may sometimes conclude at a precursor with further known synthetic pathways to a target molecule, in which case it is known as a formal synthesis. Total synthesis target molecules can be natural products, medicinally-important active ingredients, known intermediates, or molecules of theoretical interest. Total synthesis targets can also be organometallic or inorganic, though these are rarely encountered. Total synthesis projects often require a wide diversity of reactions and reagents, and subsequently requires broad chemical knowledge and training to be successful. Often, the aim is to discover a new route of synthesis for a target molecule for which there already exist known routes. Sometimes, however, no ...
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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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Glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness. The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of all brain tumors. They can either start from normal brain cells or develop from an existing low-grade astrocytoma. The diagnosis typically is made by a combination of a CT scan, MRI scan, and tissue biopsy. There is no known method of preventing the cancer. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is frequently used ...
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Prodrug
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted (ADME). Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract. A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects. History Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone. For example, salicin is a β-D-glucopyranosid ...
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Mechanism Of Action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives. In contrast, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance. Importance Elucidating the mechanism of action of novel drugs and medications is important for several reasons: * In the case of anti-infectiv ...
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Cofactor (biochemistry)
A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from ligands in that they often derive their function by remaining bound. Cofactors can be divided into two types: inorganic ions and complex organic molecules called coenzymes. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Note that some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here.) Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein. ...
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