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Ridaforolimus
Ridaforolimus (also known as AP23573 and MK-8669; formerly known as deforolimus) is an investigational targeted and small-molecule inhibitor of the protein mTOR, a protein that acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins, such as PI3K, AKT and PTEN (gene), PTEN known to be important to malignancy. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, cell division, division, metabolism, and angiogenesis. It has had promising results in a clinical trial for advanced soft tissue and bone sarcoma. Commercial arrangements Ridaforolimus is being co-developed by Merck & Co., Merck and ARIAD Pharmaceuticals. On May 5, 2010, Ariad Pharmaceuticals and Merck & Co., Merck & Company announced a clinical development and marketing agreement. With this agreement, Ariad received $125 million in upfront payments from Merck and $53 million in milestone pa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Discovery And Development Of MTOR Inhibitors
mTOR inhibitors are a drug class, class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of Phosphoinositide 3-kinase, phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs (rapamycin and its analogs), which have shown tumor responses in clinical trials against various tumor types. History The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its enzyme inhibitor, inhibitor, rapamycin. Rapamycin was first discovered in 1975 in a soil sample from Easter Island of Oceania, South Pacific, also known as Rapa Nui, from where its name is derived. Rapamycin is a macrolide, produced by the microorganism ''Streptomyces hygroscopicus'' and showed antifun ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ARIAD Pharmaceuticals
ARIAD Pharmaceuticals, Inc. was an American oncology company, now part of Takeda Oncology, which was founded in 1991 by Harvey J. Berger, M.D. and headquartered in Cambridge, Massachusetts. ARIAD engaged in the discovery, development, and commercialization of medicines for cancer patients. ARIAD’s most prominent drug discoveries include Iclusig, designed for patients with all forms of Philadelphia chromosome-positive h+chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who are resistant to or unable to tolerate other tyrosine kinase inhibitors, and brigatinib, a lung cancer drug which has completed its registration trial in ALK fusion driven non-small cell lung cancer as of June 2016 and was approved in the U.S. in April 2017. In January 2017, Takeda announced it would acquire ARIAD for $5.2 billion, expanding the company's oncology and hematology business. On February 16, 2017, Takeda Pharmaceuticals, Ltd. announced it had completed its acquisition of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTOR
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also been implicated in the control and maintenance ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals ( signal transduction). The development of therapies with specific molecular or genetic targ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Macrolides
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Rapamycin is also a macrolide and was originally developed as an antifungal, but is now used as an immunosuppressant drug and is being investigated as a potential longevity therapeutic. Macrolides are bacteriostatic in that they suppress or inhibit bacterial growth rather than killing bacteria completely. Definition In general, any macrocyclic lactone having greater than 8-membered rings are candidates for this class. The macrocycle may contain amino nitrogen, amide nitrogen (but should be differentiated from cyclopeptides), an oxazole ring, or a thiazole ring. Benzene rings are exclud ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunosuppressants
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Double-blind
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints. During the course of an experiment, a participant becomes unblinded if they deduce or otherwise obtain information that has been masked to them. For example, a patient who experiences a side effect may correc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Primary Endpoint
Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign that strongly motivates withdrawal of an individual or entity from the trial, then often termed a ''humane (clinical) endpoint''. The primary endpoint of a clinical trial is the endpoint for which the trial is powered. Secondary endpoints are additional endpoints, preferably also pre-specified, for which the trial may not be powered. Surrogate endpoints are trial endpoints that have outcomes that substitute for a clinical endpoint, often because studying the clinical endpoint is difficult, for example using an increase in blood pressure as a surrogate for death by cardiovascular disease, where strong evidence of a causal link exists. Scope In a general sense, a clinical endpoint is included in the entities of interest in a trial. The res ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Progression-free Survival
Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Similarly, "disease-free survival" is the length of time after patients have received treatment and have no detectable disease. Time to progression (TTP) does not count patients who die from other causes but is otherwise a close equivalent to PFS (unless there are many such events). The FDA gives separate definitions and prefers PFS. Background PFS is widely used as a surrogate endpoint in oncology. The definition of "progression" generally involves imaging techniques (plain radiograms, CT scans, MRI, PET scans, ultrasounds) or other aspects: biochemical progression may be defined on the basis of an increase in a tumor marker (such as CA125 for epithelia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north toward the East China Sea, Philippine Sea, and Taiwan in the south. Japan is a part of the Ring of Fire, and spans Japanese archipelago, an archipelago of List of islands of Japan, 6852 islands covering ; the five main islands are Hokkaido, Honshu (the "mainland"), Shikoku, Kyushu, and Okinawa Island, Okinawa. Tokyo is the Capital of Japan, nation's capital and largest city, followed by Yokohama, Osaka, Nagoya, Sapporo, Fukuoka, Kobe, and Kyoto. Japan is the List of countries and dependencies by population, eleventh most populous country in the world, as well as one of the List of countries and dependencies by population density, most densely populated and Urbanization by country, urbanized. About three-fourths of Geography of Japan, the c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
