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Rapamycin
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor ( PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin kinase (mTOR) inhibitor that inhibits activation of T cells and B cells by reducing their sensitivity to interleukin-2 (IL-2). It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially developed as an antifungal agent. However, this use was abandoned when it was discovered to have pote ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mechanistic Target Of Rapamycin Kinase
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 o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTOR Inhibitors
mTOR inhibitors are a 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 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 inhibitor, rapamycin. Rapamycin was first discovered in 1975 in a soil sample from Easter Island of 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 antifungal properties. Shortly after its discovery, immunosuppressive ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare, progressive and systemic disease that typically results in cystic lung destruction. It predominantly affects women, especially during childbearing years. The term sporadic LAM is used for patients with LAM not associated with tuberous sclerosis complex (TSC), while TSC-LAM refers to LAM that is associated with TSC. Signs and symptoms The average age of onset is the early to mid 30s. Exertional dyspnea (shortness of breath) and spontaneous pneumothorax (lung collapse) have been reported as the initial presentation of the disease in 49% and 46% of patients, respectively. Diagnosis is typically delayed 5 to 6 years. The condition is often misdiagnosed as asthma or chronic obstructive pulmonary disease. The first pneumothorax, or lung collapse, precedes the diagnosis of LAM in 82% of patients. The consensus clinical definition of LAM includes multiple symptoms: * Fatigue * Cough * Coughing up blood (rarely massive) * Chest pain * Chylous com ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease. TSC is caused by a mutation of either of two genes, ''TSC1'' and ''TSC2'', which code for the proteins hamartin and tuberin, respectively, with ''TSC2'' mutations accounting for the majority and tending to cause more severe symptoms. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation. Prognosis is highly variable and depends on the symptoms, but life expectancy is normal for many. The prevalence of the disease is estimated to be 7 to 12 in 100,000. The disease is often abbreviated to tuberous sclerosis, which refers to the ha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TSC2
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene. Function Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. Hamartin coded by the gene TSC1 functions as a facilitator of Hsp90 in chaperoning of Tuberin, therefore preventing its ubiquitination and degradation in the proteasome. Alternative splicing results in multiple transcript variants encoding different isoforms of the protein. Mutations in TSC2 can cause Lymphangioleiomyomatosis, a disease caused by the enlargement of tissue in the lungs, creating cysts and tumours and causing difficulty breathing. Because Tuberin regulates cell size, along with the protein Hamartin, mutations to TSC1 and TSC2 genes may prevent the control of cell growth in the lungs of individuals. Cell Pathology Cells from individuals with pathogenic mutations in the TSC2 gene displ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium '' Streptomyces tsukubensis''. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calcineurin Inhibitor
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- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Easter Island
Easter Island ( rap, Rapa Nui; es, Isla de Pascua) is an island and special territory of Chile in the southeastern Pacific Ocean, at the southeasternmost point of the Polynesian Triangle in Oceania. The island is most famous for its nearly 1,000 extant monumental statues, called '' moai'', which were created by the early Rapa Nui people. In 1995, UNESCO named Easter Island a World Heritage Site, with much of the island protected within Rapa Nui National Park. Experts disagree on when the island's Polynesian inhabitants first reached the island. While many in the research community cited evidence that they arrived around the year 800, there is compelling evidence presented in a 2007 study that places their arrival closer to 1200. The inhabitants created a thriving and industrious culture, as evidenced by the island's numerous enormous stone ''moai'' and other artifacts. However, land clearing for cultivation and the introduction of the Polynesian rat led to gradual defo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Streptomyces Hygroscopicus
''Streptomyces hygroscopicus'' is a bacterial species in the genus ''Streptomyces''. It was first described by Hans Laurits Jensen in 1931. Biochemistry Cultures of different strains of ''S. hygroscopicus'' can be used to produce a number of chemical compounds or enzymes. Small molecules Immunosuppressants Sirolimus (also known as rapamycin) is an immunosuppressant that has been isolated from ''S. hygroscopicus'' from soil samples from Easter Island. Ascomycin can be used to treat autoimmune diseases and skin diseases, and can help prevent rejection after an organ transplant. Antibiotics The antibiotics geldanamycin, hygromycin B, nigericin, validamycin, and cyclothiazomycin are found in ''S. hygroscopicus''. Experimental cancer drugs Indolocarbazoles can be found in ''S. hygroscopicus'' . Anthelmintics and insecticides Milbemycin and milbemycin oxime can be found in ''S. hygroscopicus'' cultures. Herbicide ''S. hygroscopicus'' also produces the natur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunosuppressant
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis is the assessment that a particular edicalcondition is present while an indication is a reason for use. The opposite of an indication is a contraindication, a reason to withhold a certain medical treatment because the risks of treatment clearly outweigh the benefits. In the United States, indications for prescription drugs are approved by the FDA. Indications are included in the Indications and Usage section of the Prescribing Information. The primary role of this section of labeling is to enable health care practitioners to readily identify appropriate therapies for patients by clearly communicating the drug’s approved indication(s). The Indications and Usage section states the disease or condition, or manifestation or symptoms the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Topical Administration
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word ''topical'' derives from Greek τοπικός ''topikos'', "of a place". Justification Topical drug delivery is a route of administering drugs via the skin to provide topical therapeutic effects. As skin is one of the largest and most superficial organs in the human body, pharmacists utilise it to deliver various drugs ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
