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Resatorvid
Resatorvid (TAK-242) is a cyclohexane derivative that was invented by scientists at Takeda in a drug discovery campaign to identify inhibitors of the receptor TLR4. It binds directly to cysteine residue 747 intracellularly, preventing TLR4 binding with TIRAP and thus preventing downstream signal transduction. A randomized, double-blinded Phase III trial of resatorvid in sepsis was halted early due to lack of efficacy, and the compound has become a widely used tool compound in biological research. It has antiinflammatory and neuroprotective effects in preclinical models. It has been explored in preclinical studies of several forms of cancer, including multiple myeloma, breast cancer, and ovarian cancer, and has been suggested for study in skin cancers. Efforts have been made to improve resatorvid by making prodrugs and deuterated derivatives. See also * M62812 * TLR4-IN-C34 TLR4-IN-C34 (or C34) is a drug which acts as a potent and selective antagonist of Toll-lik ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TLR4-IN-C34
TLR4-IN-C34 (or C34) is a drug which acts as a potent and selective antagonist of Toll-like receptor 4 (TLR4). In animal studies it blocks TLR4-mediated cytokine release and has antiinflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechani ... effects. See also * M62812 * Resatorvid References Receptor antagonists Acetamides Oxygen heterocycles {{pharm-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
M62812
M62812 is a drug which acts as a potent and selective antagonist of toll-like receptor 4 (TLR4). In animal studies it blocks TLR4-mediated cytokine release and has antiinflammatory effects, showing efficacy in animal models of arthritis and septic shock. See also * TLR4-IN-C34 * Resatorvid * VGX-1027 VGX-1027 (GIT-27) is a drug which acts as an immunomodulator. It acts by blocking downstream signalling of the Toll-like receptors TLR2, TLR4 and TLR6, and thereby reducing production of various cytokines, including interleukins and TNF-α. In a ... References Receptor antagonists Benzothiazoles Anilines Amines {{pharm-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Toll-like Receptor 4
Toll-like receptor 4 (TLR4), also designated as CD284 (cluster of differentiation 284), is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approximately 95 kDa that is encoded by the ''TLR4'' gene. TLR4 belongs to the toll-like receptor family which is representative of the pattern recognition receptors (PRR), so named for their ability to recognize evolutionarily conserved components of microorganisms (bacteria, viruses, fungi and parasites) called pathogen-associated molecular patterns (PAMPs). The recognition of a PAMP by a PRR triggers rapid activation of the innate immunity essential to fight infectious diseases. TLR4 is expressed in immune cells mainly of myeloid origin, including monocytes, macrophages and dendritic cells (DC). It is also expressed at a lower level on some non-immune cells, including epithelium, endothelium, placental cells and beta cells in Langerhans isle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sepsis
Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and symptoms include fever, tachycardia, increased heart rate, hyperventilation, increased breathing rate, and mental confusion, confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or dysuria, painful urination with a pyelonephritis, kidney infection. The very young, old, and people with a immunodeficiency, weakened immune system may not have any symptoms specific to their infection, and their hypothermia, body temperature may be low or normal instead of constituting a fever. Severe sepsis may cause organ dysfunction and significantly reduced blood flow. The presence of Hypotension, low blood pressure, high blood Lactic acid, lactate, or Oliguria, low urine output may suggest poor blood flow. Se ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Deuterated Drug
A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs may have significantly lower rates of metabolism, and hence a longer half-life. Mode of action Hydrogen is a chemical element with an atomic number of 1. It has one proton and one electron. Deuterium is the heavier naturally-occurring stable isotope of hydrogen. Deuterium was discovered by Harold Urey in 1931, for which he received the Nobel Prize in 1934. The deuterium isotope effect has become an important tool in the elucidation of the mechanism of chemical reactions. Deuterium contains one proton, one electron, and a neutron, effectively doubling the mass of the deuterium isotope without changing its properties significantly. However, the C–D bond is a bit shorter, and it has reduced electronic polarizability and less hyperconjugati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prodrugs
A prodrug is a pharmacologically inactive Pharmaceutical drug, medication or compound that, after Drug administration, intake, is Drug metabolism, 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 a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. Mechanisms in neurodegeneration, and associated treatments It is a widely explored treatment option for many central nervous system disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption (i.e. methamphetamine overdoses). Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antiinflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechanisms of inflammation, as opposed to opioids, which affect the central nervous system to block pain. Common anti-inflammatory drugs include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antileukotrienes, and monoclonal antibodies. Drugs Clinically approved Nonsteroidal anti-inflammatory drugs NSAIDs alleviate pain by counteracting the cyclooxygenase (COX) enzyme involved in pain mechanisms. Some common examples of NSAIDs are aspirin, ibuprofen, and naproxen. Selective COX-2 inhibitors, such as celecoxib, block the enzymatic conversion of arachidonic acid into prostaglandin, inhibiting inflammation and pain. Analgesics commonly associated with anti-inflammatory drugs, such as acetaminophen (paracetamol), have no periph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tool Compound
A tool is an object that can extend an individual's ability to modify features of the surrounding environment or help them accomplish a particular task. Although many animals use simple tools, only human beings, whose use of stone tools dates back hundreds of millennia, have been observed using tools to make other tools. Early human tools, made of such materials as stone, bone, and wood, were used for the preparation of food, hunting, the manufacture of weapons, and the working of materials to produce clothing and useful artifacts and crafts such as pottery, along with the construction of housing, businesses, infrastructure, and transportation. The development of metalworking made additional types of tools possible. Harnessing energy sources, such as animal power, wind, or steam, allowed increasingly complex tools to produce an even larger range of items, with the Industrial Revolution marking an inflection point in the use of tools. The introduction of widespread automation in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclohexane
Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colourless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclohexane is mainly used for the industrial production of adipic acid and caprolactam, which are Precursor (chemistry), precursors to nylon. Cyclohexyl () is the alkyl substituent of cyclohexane and is abbreviated Cy. Production Cyclohexane is one of components of naphtha, from which it can be extracted by advanced distillation methods. Distillation is usually combined with isomerization of methylcyclopentane, a similar component extracted from naphtha by similar methods. Together, these processes cover only a minority (15-20%) of the modern industrial demand, and are complemented by synthesis. Modern industrial synthesis On an industrial scale, cyclohexane is produced by hydrogenation of benzene in the presence of a Raney nickel catalyst. Prod ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Takeda Pharmaceutical Company
The is a Japanese multinational pharmaceutical company. It is the third largest pharmaceutical company in Asia, behind Sinopharm and Shanghai Pharmaceuticals, and one of the top 20 largest pharmaceutical companies in the world by revenue (top 10 following its merger with Shire). The company has over 49,578 employees worldwide and achieved US$19.299 billion in revenue during the 2018 fiscal year. The company is focused on oncology, rare diseases, neuroscience, gastroenterology, plasma-derived therapies and vaccines. Its headquarters is located in Chuo-ku, Osaka, and it has an office in Nihonbashi, Chuo, Tokyo. In January 2012, Fortune Magazine ranked the Takeda Oncology Company as one of the 100 best companies to work for in the United States. As of 2015, Christophe Weber was appointed as the CEO and president of Takeda. History Founding and initial acquisitions (1781–2010) Takeda Pharmaceuticals was founded in 1781, and was incorporated on January 29, 1925. One ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Signal Transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), receptors, although in some cases the term sensor is used. The changes elicited by ligand (biochemistry), ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a Cell signaling#Signaling pathways, signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription (biology), transcription or translation (biology), translation of genes, and post-translational modification, post-translational and conformational changes in proteins, as well as changes in their location. These molecula ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
