Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor
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Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor
Not to be confused with '' Factor Inhibiting HIF Asparaginyl Hydroxylase Inhibitors'' Hypoxia-inducible factor prolyl hydroxylase Inhibitors (HIF-PHIs) also known as hypoxia-inducible factor stabilizers (HIF stabilizers) are members of a mostly experimental class of drugs that act by inhibiting hypoxia-inducible factor-proline dioxygenase (HIF prolyl-hydroxylase) which is responsible to break down the hypoxia-inducible factor (HIF) under conditions of normal oxygen concentrations. they had been investigated in in cell models for the treatment of anemia, chronic kidney disease (CKD), ischemia including ischemia of the heart tissue, cancer, and others. Research conducted in mice suggests that they may increase hippocampal memory by increasing erythropoietin expression. research focuses mainly on anemia associated with CKD, and to some extent on ischemia. One drug of this class (roxadustat) is marketed in China and Japan for the treatment of anaemia in CKD patients. Examples ...
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Roxadustat
Roxadustat, sold under the brand name Evrenzo, is an anti-anemia medication. Roxadustat is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of erythropoietin and stimulates production of hemoglobin and red blood cells. It was investigated in clinical trials for the treatment of anemia caused by chronic kidney disease (CKD). It is taken by mouth. The drug was developed by FibroGen, in partnership with AstraZeneca. The most common side effects include hypertension (high blood pressure), vascular access thrombosis (formation of blood clots in the blood vessels associated with dialysis), diarrhea, peripheral edema (swelling especially of the ankles and feet), hyperkalemia (high blood potassium levels) and nausea (feeling sick). Roxadustat received its first global approval in China on 17 December 2018, for the treatment of anemia caused by CKD in patients who are dialysis-dependent. It was approved in Japan in 2019, for the treatment of anemia caused by CKD in ...
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Erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Low levels of EPO (around 10  mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease. Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with the peritubular capillary and proximal convoluted tubule. It is also produced in perisinusoidal cells in the liver. Liver production predominates in the fetal and perinatal period; renal production predominates in adulthood. It is homologous with thrombopoietin. Exogenous erythropoietin, recombinant human erythropoietin (rhEPO), ...
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Vadadustat
Vadadustat, sold under the brand name Vafseo is a medication used for the treatment of symptomatic anemia associated with chronic kidney disease. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The most common side effects include thromboembolic events (problems due to the formation of blood clots in the blood vessels), diarrhea, and hypertension (high blood pressure). Vadadustat was approved for medical use in the European Union in April 2023. Medical uses Vadadustat is indicated for the treatment of symptomatic anemia associated with chronic kidney disease in adults on chronic maintenance dialysis. Society and culture Legal status On 23 February 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vafseo, intended ...
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Molidustat
Molidustat is a drug which acts as an HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells. It is in Phase III clinical trials for the treatment of anemia caused by chronic kidney disease. Due to its potential applications in athletic doping, it has also been incorporated into screens for performance-enhancing drugs. Veterinary use Molidustat is indicated for the control of nonregenerative anemia associated with chronic kidney disease in cats.https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/13903 The US 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 respon ... (FDA) conditionally approved it in May 2023. The reasonable ex ...
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Enarodustat
Enarodustat (development code JTZ-951; brand name Enaroy) is a drug used for the treatment of anemia, especially when associated with chronic kidney disease (CKD). Enarodustat functions as a inhibitor of hypoxia inducible factor-proly hydroxylase (HIF-PH). The drug was approved in September 2020 in Japan for anemia associated with CKD and is currently in clinical development Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regu ... in the United States and South Korea. The drug is being developed by Japan Tobacco and JW Pharmaceutical. References Drugs acting on the blood and blood forming organs Alpha-Amino acids Triazolopyridines Secondary amino acids {{blood-drug-stub ...
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Desidustat
Desidustat (INN, also known as ZYAN1) is a drug for the treatment of anemia of chronic kidney disease. This drug with the brand name Oxemia is discovered and developed by Zydus Life Sciences. Desidustat reduces the requirement of recombinant erythropoietin requirement in anemia, and decreases EPO-resistance, by reducing IL-6, IL-1β, and anti-EPO antibodies. The subject expert committee of CDSCO has recommended the grant of permission for manufacturing and marketing of Desidustat 25 mg and 50 mg tablets in India,based on some conditions related to package insert, phase 4 protocols, prescription details, and GCP. Clinical trials on desidustat have been done in India and Australia. In a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study, a mean hemoglobin increase of 1.57, 2.22, and 2.92 g/dL in desidustat 100, 150, and 200 mg arms, respectively, was observed. The Phase 3 clinical trials were conducted in chronic k ...
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Daprodustat
Daprodustat, sold under the brand name Duvroq among others, is a medication that is used for the treatment of anemia due to chronic kidney disease. It is a hypoxia-inducible factor prolyl hydroxylase inhibitor. It is taken by mouth. The most common side effects include high blood pressure, thrombotic vascular events, abdominal pain, dizziness and allergic reactions.  Daprodustat was approved for medical use in Japan in June 2020, and in the United States in February 2023. It is the first oral treatment for anemia caused by chronic kidney disease for adults. Medical uses Daprodustat is indicated for the treatment of anemia due to chronic kidney disease. History Daprodustat increases erythropoietin levels. The effectiveness of daprodustat was established in a randomized study of 2,964 adult participants receiving dialysis. In this study, participants received either oral daprodustat or injected recombinant human erythropoietin (a standard of care treatment for people wit ...
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Astellas
is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of and . On February 5, 2020, the company announced management changes effective from April 1, 2020. 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. Recent times and mergers 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 pharmaceut ...
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Roxadustat
Roxadustat, sold under the brand name Evrenzo, is an anti-anemia medication. Roxadustat is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of erythropoietin and stimulates production of hemoglobin and red blood cells. It was investigated in clinical trials for the treatment of anemia caused by chronic kidney disease (CKD). It is taken by mouth. The drug was developed by FibroGen, in partnership with AstraZeneca. The most common side effects include hypertension (high blood pressure), vascular access thrombosis (formation of blood clots in the blood vessels associated with dialysis), diarrhea, peripheral edema (swelling especially of the ankles and feet), hyperkalemia (high blood potassium levels) and nausea (feeling sick). Roxadustat received its first global approval in China on 17 December 2018, for the treatment of anemia caused by CKD in patients who are dialysis-dependent. It was approved in Japan in 2019, for the treatment of anemia caused by CKD in ...
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National Library Of Medicine
The United States National Library of Medicine (NLM), operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health. Its collections include more than seven million books, journals, technical reports, manuscripts, microfilms, photographs, and images on medicine and related sciences, including some of the world's oldest and rarest works. The current director of the NLM is Patricia Flatley Brennan.National Library of Medicine Welcomes New Director Dr. Patricia Flatley Brennan
. ''National Library of Medicine''. August 15, 2016.


History

The precursor o ...
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Hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper (also called ''Ammon's horn''), and the dentate gyrus. In Alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result from ...
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Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind reversibly or irreversibly. Irreversible inhibitors form a chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind non-covalently and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Reve ...
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