Erythropoietin, 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 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 include any anemia, and hypoxemia due to chronic lung disease.
Polycythemia is a laboratory finding in which the hematocrit and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythrocytosis, and there is significant overlap in the two findings, but the terms are not the same: polycythemia describes any increase in hematocrit and/or hemoglobin, while erythrocytosis describes an increase specifically in the number of red blood cells in the blood.
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure, bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization.
Blood doping is a form of doping in which the number of red blood cells in the bloodstream is boosted in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the blood can improve an athlete's aerobic capacity (VO2 max) and endurance. Blood doping can be achieved by making the body produce more red blood cells itself using drugs, giving blood transfusions either from another person or back to the same individual, or by using blood substitutes.
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals.
Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy.
Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type 2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease.
Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In these situations they decrease the need for blood transfusions. The different agents are more or less equivalent. They are given by injection.
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2S, 4R)-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome.
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the EGLN1 gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase.
Continuous erythropoietin receptor activator (CERA) is the generic term for drugs in a new class of third-generation erythropoiesis-stimulating agents (ESAs). In the media, these agents are commonly referred to as 'EPO', short for erythropoietin. CERAs have an extended half-life and a mechanism of action that promotes increased stimulation of erythropoietin receptors compared with other ESAs.
Not to be confused with Factor Inhibiting HIF Asparaginyl Hydroxylase Inhibitors
Peginesatide, developed by Affymax and Takeda, is an erythropoietic agent, a functional analog of erythropoietin.
Hypoxia-inducible factor-proline dioxygenase (EC 1.14.11.29, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction
Vadadustat, sold under the brand name Vafseo is a medication used for the treatment of symptomatic anemia associated with chronic kidney disease.
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.
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.
Desidustat 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 kidney disease patients which were not on dialysis as well as on dialysis. Desidustat is developed for the treatment of anemia as an oral tablet, where currently injections of erythropoietin and its analogues are drugs of choice. Desidustat is a HIF prolyl-hydroxylase inhibitor. In preclinical studies, effects of desidustat was assessed in normal and nephrectomized rats, and in chemotherapy-induced anemia. Desidustat demonstrated hematinic potential by combined effects on endogenous erythropoietin release and efficient iron utilization. Desidustat can also be useful in treatment of anemia of inflammation since it causes efficient erythropoiesis and hepcidin downregulation. In January 2020, Zydus entered into licensing agreement with China Medical System (CMS) Holdings for development and commercialization of desidustat in Greater China. Under the license agreement, CMS will pay Zydus an initial upfront payment, regulatory milestones, sales milestones and royalties on net sales of the product. CMS will be responsible for development, registration and commercialization of desidustat in Greater China. It has been observed that desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines like IL-6 and oxidative stress A clinical trial to evaluate the efficacy and safety of desidustat tablet for the management of Covid-19 patients is ongoing in Mexico, wherein desidustat has shown to prevent acute respiratory distress syndrome (ARDS) by inhibiting IL-6. Zydus has also received approval from the US FDA to initiate clinical trials of desidustat in chemotherapy Induced anemia (CIA).
Belzutifan, sold under the brand name Welireg, is an anti-cancer medication used for the treatment of von Hippel–Lindau disease-associated renal cell carcinoma. It is taken by mouth. Belzutifan is an hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor.
Enarodustat 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).
