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Gilteritinib
Gilteritinib, sold under the brand name Xospata, is an anti-cancer drug. Mechanism of action Gilteritinib acts as an inhibitor of FLT3, hence it is a tyrosine kinase inhibitor. History Gilteritinib was developed by Astellas Pharma. In April 2018, Astellas filed a new drug application with the Food and Drug Administration for gilteritinib for the treatment of adult patients with FLT3 mutation–positive (both ITD and TKD) relapsed or refractory acute myeloid leukemia (AML). In November 2018, the FDA approved gilteritinib for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. Gilteritinib was granted orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ... status by the U.S. FD ...
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FLT3 Mutation
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3 with fms standing for "feline McDonough sarcoma"), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L). It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells. The ''FLT3'' gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis. Structure FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane ...
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Astellas Pharma
is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of and . Astellas is a member of the Mitsubishi UFJ Financial Group (MUFJ) keiretsu. History Early foundations Fujisawa Shoten was started in 1894 by Tomokichi Fujisawa in Osaka, and was renamed Fujisawa Pharmaceutical Co. in 1943. Yamanouchi Yakuhin Shokai was started in 1923 by Kenji Yamanouchi in Osaka. The company was renamed Yamanouchi Pharmaceutical Co. in 1940 and moved to Tokyo in 1942. Both companies started their overseas expansion at about the same time, opening offices in Taiwan in 1962 and 1963, respectively, and in the United States and Europe from 1977 onwards. Mergers and acquisitions Fujisawa acquired Lyphomed in 1990 and thereafter established its US R&D center in Deerfield, Illinois. Yamanouchi's R&D center in Leiderdorp was established with the acquisition of the pharmaceutical division of Royal Gist Brocades in 1991. Fujisawa and Yamanouchi combined in a "merg ...
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Oral Administration
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administration can be easier and less painful than other routes of administration, such as Injection (medicine), 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 able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth". The expression is used in medicine to describe a treatment that is taken orally (but not ...
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Tyrosine Kinase Inhibitors
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis. They are also called tyrphostins, the short name for "tyrosine phosphorylation inhibitor", originally coined in a 1988 publication, which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphor ...
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Piperidines
Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic compound, heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor described as objectionable, typical of amines. The name comes from the genus name ''Piper (genus), Piper'', which is the Latin word for Black pepper, pepper. Although piperidine is a common organic compound, it is best known as a representative structure element within many pharmaceuticals and alkaloids, such as natural-occurring Solenopsin, solenopsins. Production Piperidine was first reported in 1850 by the Scottish chemist Thomas Anderson (chemist), Thomas Anderson and again, independently, in 1852 by the French chemist Auguste André Thomas Cahours, Auguste Cahours, who named it. Both of them obtained piperidine by reacting piperine with nitric acid. Industrially, piperidine is produced by the hydrogenation of p ...
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Pyrazines
Pyrazine is a heterocyclic aromatic organic compound with the chemical formula C4H4N2. It is a symmetrical molecule with point group D2h. Pyrazine is less basic than pyridine, pyridazine and pyrimidine. It is a ''"deliquescent crystal or wax-like solid with a pungent, sweet, corn-like, nutty odour"''. Pyrazine and a variety of alkylpyrazines are flavor and aroma compounds found in baked and roasted goods. Tetramethylpyrazine (also known as ligustrazine) is reported to scavenge superoxide anions and decrease nitric oxide production in human granulocytes. Synthesis Many methods exist for the organic synthesis of pyrazine and its derivatives. Some of these are among the oldest synthesis reactions still in use. In the Staedel–Rugheimer pyrazine synthesis (1876), 2-chloroacetophenone is reacted with ammonia to the amino ketone, then condensed and then oxidized to a pyrazine. A variation is the Gutknecht pyrazine synthesis (1879) also based on this selfcondensation, but dif ...
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Therapeutic Goods Administration
The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health, Disability and Ageing, the TGA regulates the safety, quality, efficacy and advertising in Australia of therapeutic goods (which comprise medicines, medical devices, biologicals and certain other therapeutic goods). Therapeutic goods include goods that are represented to have a therapeutic effect, are included in a class of goods the sole or principal use of which is (or ordinarily is) a therapeutic use, or are otherwise determined to be a therapeutic good through a legislative instrument under the ''Therapeutic Goods Act 1989.'' Goods that are therapeutic goods must be entered on the Australian Register of Therapeutic Goods (ARTG), or otherwise be the subject of an exemption, approval or authority by the TGA under the ''Therapeutic Goods Act 1989'', ''Therapeutic Goods Regulations 1990'' or ''Therapeutic Goods (Medical Dev ...
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Orphan Drug
An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the conditions. The conditions that orphan drugs are used to treat are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy that depends on the legislation (if there is any) of the country. Designation of a drug as an orphan drug has yielded medical breakthroughs that might not otherwise have been achieved, due to the economics of drug medical research, research and development. Examples of this can be that in the U.S. and the EU, it is easier to gain marketing approval for an orphan drug. There may be other financial incentives, such as an extended period of exclusivity, during which the producer has sole rights to market the drug. All are intended to en ...
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Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C). However, the agency also enforces other laws, notably Section 361 of the Public Health Service Act as well as associated regulations. Much of this regulatory-enforcement work is ...
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Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Symptoms may include Fatigue, feeling tired, shortness of breath, Bruise, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a anemia, drop in red blood cells, thrombocytopenia, platelets, and normal leukopenia, white blood cells. Diagnosis is generally based on bone marrow aspiration and specific bl ...
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