| EPO |
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| Available structures |
| PDB |
Ortholog search: PDBe RCSB |
| List of PDB id codes |
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1BUY, 1CN4, 1EER
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| Identifiers |
| Aliases |
EPO, EP, MVCD2, erythropoietin |
| External IDs |
OMIM: 133170 MGI: 95407 HomoloGene: 624 GeneCards: 2056 |
| Gene ontology |
| Molecular function |
• erythropoietin receptor binding
• hormone activity
• protein kinase activator activity
• protein binding
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| Cellular component |
• extracellular space
• extracellular region
• cell surface
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| Biological process |
• erythrocyte maturation
• negative regulation of cation channel activity
• response to interleukin-1
• response to hypoxia
• negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress
• response to nutrient
• response to salt stress
• negative regulation of erythrocyte apoptotic process
• response to testosterone
• regulation of transcription from RNA polymerase II promoter
• response to hyperoxia
• positive regulation of Ras protein signal transduction
• ageing
• positive regulation of tyrosine phosphorylation of Stat5 protein
• negative regulation of apoptotic process
• negative regulation of transcription from RNA polymerase II promoter
• response to electrical stimulus
• blood circulation
• response to estrogen
• cellular hyperosmotic response
• positive regulation of transcription, DNA-templated
• positive regulation of DNA replication
• response to vitamin A
• response to lipopolysaccharide
• acute-phase response
• peptidyl-serine phosphorylation
• response to axon injury
• hemoglobin biosynthetic process
• positive regulation of neuron differentiation
• positive regulation of cell proliferation
• regulation of transcription from RNA polymerase II promoter in response to hypoxia
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of neuron projection development
• negative regulation of calcium ion transport into cytosol
• erythrocyte differentiation
• negative regulation of myeloid cell apoptotic process
• activation of protein kinase activity
• cellular response to hypoxia
• embryo implantation
• signal transduction
• positive regulation of activated T cell proliferation
• positive regulation of protein kinase activity
• negative regulation of neuron death
• apoptotic process
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| Sources:Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
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| Ensembl |
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| UniProt |
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| RefSeq (mRNA) |
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| RefSeq (protein) |
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| Location (UCSC) |
Chr 7: 100.72 – 100.72 Mb |
Chr 5: 137.48 – 137.53 Mb |
| PubMed search |
[1] |
[2] |
| Wikidata |
| View/Edit Human |
View/Edit Mouse |
Erythropoietin ( or ;[1][2][3] from Greek: ἐρυθρός, erythros 'red' and ποιεῖν, poiein 'make'), also known as EPO, hematopoietin, or hemopoietin, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine (protein signaling molecule) for erythrocyte (red blood cell) precursors in the bone marrow. Human EPO has a molecular weight of 34 kDa.
Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and proximal convoluted tubule. It is also produced in perisinusoidal cells in the liver. While liver production predominates in the fetal and perinatal period, renal production is predominant during adulthood.
Exogenous erythropoietin, or recombinant human erythropoietin (rhEPO), is produced by recombinant DNA technology in cell culture. Several different pharmaceutical agents are available with a variety of glycosylation patterns, and are collectively called erythropoiesis-stimulating agents (ESA). The specific details for labeled use vary between the package inserts, but ESAs have been used in the treatment of anemia in chronic kidney disease, anemia in myelodysplasia, and in anemia from cancer chemotherapy. Boxed warnings include a risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence.[4] rhEPO has been used illicitly as a performance-enhancing drug;[5] it can often be detected in blood, due to slight differences from the endogenous protein, for example, in features of posttranslational modification.
Contents
- 1 Function
- 1.1 Red blood cell production
- 1.2 Nonhematopoietic roles
- 2 Mechanism of action
- 3 Synthesis and regulation
- 4 Medical uses
- 5 History
- 6 See also
- 7 References
- 8 Further reading
- 9 External links
Function
Red blood cell production
Erythropoietin is an essential hormone for red blood cell production. Without it, definitive erythropoiesis does not take place. Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation. Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in humans) by promoting their survival through protecting these cells from apoptosis.
Erythropoietin is the primary erythropoietic factor that cooperates with various other growth factors (e.g., IL-3, IL-6, glucocorticoids, and SCF) involved in the development of erythroid lineage from multipotent progenitors. The burst-forming unit-erythroid (BFU-E) cells start erythropoietin receptor expression and are sensitive to erythropoietin. Subsequent stage, the colony-forming unit-erythroid (CFU-E), expresses maximal erythropoietin receptor density and is completely dependent on erythropoietin for further differentiation. Precursors of red cells, the proerythroblasts and basophilic erythroblasts also express erythropoietin receptor and are therefore affected by it.
Nonhematopoietic roles
Erythropoietin was reported to have a range of actions beyond stimulation of erythropoiesis including vasoconstriction-dependent hypertension, stimulating angiogenesis, and promoting cell survival via activation of Epo receptors resulting in anti-apoptotic effects on ischemic tissues. However this proposal is controversial with numerous studies showing no effect.[6] It is also inconsistent with the low levels of Epo receptors on those cells. Clinical trials in humans with ischemic heart, neural and renal tissues have not demonstrated the same benefits seen in animals. In addition some research studies have shown its neuroprotective effect on the diabetic neuropathy, however these data were not confirmed in the clinical trial have been conducted on the deep peroneal, superficial preoneal, tibial, and sural nerves.[7]
Mechanism of action
Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR).[8][9]
EPO is highly glycosylated (40% of total molecular weight), with half-life in blood around five hours. EPO's half-life may vary between endogenous and various recombinant versions. Additional glycosylation or other alterations of EPO via recombinant technology have led to the increase of EPO's stability in blood (thus requiring less frequent injections). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signaling cascade. High level erythropoietin receptor expression is localized to erythroid progenitor cells. While there are reports that EPO receptors are found in a number of other tissues, such as heart, muscle, kidney and peripheral/central nervous tissue, those results are confounded by nonspecificity of reagents such as anti-EpoR antibodies. In controlled experiments, EPO receptor is not detected in those tissues. In the bloodstream, red cells themselves do not express erythropoietin receptor, so cannot respond to EPO. However, indirect dependence of red cell longevity in the blood on plasma erythropoietin levels has been reported, a process termed neocytolysis.[citation needed]
Synthesis and regulation
Erythropoietin levels in blood are quite low in the absence of anemia, at around 10 mU/ml. However, in hypoxic stress, EPO production may increase up to 1000-fold, reaching 10,000 mU/ml of blood. In adults, EPO is synthesized mainly by interstitial cells in the peritubular capillary bed of the renal cortex, with additional amounts being produced in the liver.[10][11][12] Regulation is believed to rely on a feedback mechanism measuring blood oxygenation and iron availability.[13] Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and proteosomally digested in the presence of oxygen and iron.
Medical uses
Main article: Erythropoiesis-stimulating agent
Erythropoietins available for use as therapeutic agents are produced by recombinant DNA technology in cell culture, and include Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); they are used in treating anemia resulting from chronic kidney disease, chemotherapy induced anemia in patients with cancer, inflammatory bowel disease (Crohn's disease and ulcerative colitis)[14] and myelodysplasia from the treatment of cancer (chemotherapy and radiation). The package inserts include boxed warnings of increased risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence, particularly when used to increase the hemoglobin levels to more than 11 to 12 g/dl.[4]
History
In 1905, Paul Carnot, a professor of medicine in Paris, and his assistant, Clotilde Deflandre, proposed the idea that hormones regulate the production of red blood cells. After conducting experiments on rabbits subject to bloodletting, Carnot and Deflandre attributed an increase in red blood cells in rabbit subjects to a hemotropic factor called hemopoietin. Eva Bonsdorff and Eeva Jalavisto continued to study red cell production and later called the hemopoietic substance 'erythropoietin'. Further studies investigating the existence of EPO by K.R. Reissman and Allan J. Erslev (Thomas Jefferson Medical College) demonstrated that a certain substance, circulated in the blood, is able to stimulate red blood cell production and increase hematocrit. This substance was finally purified and confirmed as erythropoietin, opening doors to therapeutic uses for EPO in diseases such as anemia.[13][15]
Hematologist John Adamson and nephrologist Joseph W. Eschbach looked at various forms of renal failure and the role of the natural hormone EPO in the formation of red blood cells. Studying sheep and other animals in the 1970s, the two scientists helped establish that EPO stimulates the production of red cells in bone marrow and could lead to a treatment for anemia in humans. In 1968, Goldwasser and Kung began work to purify human EPO, and managed to purify milligram quantities of over 95% pure material by 1977.[16] Pure EPO allowed the amino acid sequence to be partially identified and the gene to be isolated.[13] Later, a researcher[specify] at Columbia University discovered a way to synthesize EPO. Columbia University patented the technique and licensed it to Amgen.[citation needed]
In the 1980s, Adamson, Joseph W. Eschbach, Joan C. Egrie, Michael R. Downing and Jeffrey K. Browne conducted a clinical trial at the Northwest Kidney Centers for a synthetic form of the hormone, Epogen, produced by Amgen. The trial was successful, and the results were published in the New England Journal of Medicine in January 1987.[17]
In 1985, Lin et al isolated the human erythropoietin gene from a genomic phage library and were able to characterize it for research and production.[18] Their research demonstrated the gene for erythropoietin encoded the production of EPO in mammalian cells that is biologically active in vitro and in vivo. The industrial production of recombinant human erythropoietin (rhEpo) for treating anemia patients would begin soon after.
In 1989, the US Food and Drug Administration approved the hormone Epogen, which remains in use today.[19]
See also
- Hemopoietic growth factors
- Jehovah's Witnesses and blood transfusions
References
- ^ "Erythropoietin". Merriam-Webster Dictionary.
- ^ "Erythropoietin". Dictionary.com Unabridged. Random House.
- ^ "erythropoietin - definition of erythropoietin in English from the Oxford dictionary". OxfordDictionaries.com. Retrieved 2016-01-20.
- ^ a b "Safety Labeling Changes: Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa)". MedWatch: The FDA Safety Information and Adverse Event Reporting Program. United States Food and Drug Administration. August 11, 2011.
- ^ Momaya A, Fawal M, Estes R (April 2015). "Performance-enhancing substances in sports: a review of the literature". Sports Med. 45 (4): 517–531. doi:10.1007/s40279-015-0308-9. PMID 25663250.
- ^ Elliott S, Sinclair AM (2012). "The effect of erythropoietin on normal and neoplastic cells". Biologics 6: 163–89. doi:10.2147/BTT.S32281. PMC 3402043. PMID 22848149.
- ^ Hosseini-Zare MS, Dashti-Khavidaki S, Mahdavi-Mazdeh M, Ahmadi F, Akrami S (2012). "Peripheral neuropathy response to erythropoietin in type 2 diabetic patients with mild to moderate renal failure". Clinical Neurology and Neurosurgery 114 (6): 663–7. doi:10.1016/j.clineuro.2012.01.007. PMID 22296650.
- ^ Middleton SA, Barbone FP, Johnson DL, Thurmond RL, You Y, McMahon FJ, Jin R, Livnah O, Tullai J, Farrell FX, Goldsmith MA, Wilson IA, Jolliffe LK (1999). "Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide". The Journal of Biological Chemistry 274 (20): 14163–9. doi:10.1074/jbc.274.20.14163. PMID 10318834.
- ^ Livnah O, Johnson DL, Stura EA, Farrell FX, Barbone FP, You Y, Liu KD, Goldsmith MA, He W, Krause CD, Pestka S, Jolliffe LK, Wilson IA (1998). "An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation". Nature Structural Biology 5 (11): 993–1004. doi:10.1038/2965. PMID 9808045.
- ^ Jacobson LO, Goldwasser E, Fried W, Plzak L (1957). "Role of the kidney in erythropoiesis". Nature 179 (4560): 633–4. doi:10.1038/179633a0. PMID 13418752.
- ^ Fisher JW, Koury S, Ducey T, Mendel S (1996). "Erythropoietin production by interstitial cells of hypoxic monkey kidneys". British Journal of Haematology 95 (1): 27–32. doi:10.1046/j.1365-2141.1996.d01-1864.x. PMID 8857934.
- ^ Barrett, Kim E.; Barman, Susan M.; Boitano, Scott; Brooks, Heddwen (eds.). Ganong's review of Medical Physiology (24th ed.). McGraw Hill. p. 709. ISBN 978-1-25-902753-6.
- ^ a b c Jelkmann W (2007). "Erythropoietin after a century of research: younger than ever". European Journal of Haematology 78 (3): 183–205. doi:10.1111/j.1600-0609.2007.00818.x. PMID 17253966.
- ^ Liu S, Ren J, Hong Z, Yan D, Gu G, Han G, Wang G, Ren H, Chen J, Li J (2013). "Efficacy of erythropoietin combined with enteral nutrition for the treatment of anemia in Crohn's disease: a prospective cohort study". Nutrition in Clinical Practice 28 (1): 120–7. doi:10.1177/0884533612462744. PMID 23064018.
- ^ Höke A (2005). Erythropoietin and the Nervous System. Berlin: Springer. ISBN 0-387-30010-4. OCLC 64571745. [page needed]
- ^ Miyake T, Kung CK, Goldwasser E (1977). "Purification of human erythropoietin". The Journal of Biological Chemistry 252 (15): 5558–64. PMID 18467.
- ^ Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987). "Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial". The New England Journal of Medicine 316 (2): 73–8. doi:10.1056/NEJM198701083160203. PMID 3537801.
- ^ Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z (1985). "Cloning and expression of the human erythropoietin gene". Proceedings of the National Academy of Sciences of the United States of America 82 (22): 7580–4. doi:10.1073/pnas.82.22.7580. PMC 391376. PMID 3865178.
- ^ Template:Http://pi.amgen.com/united states/epogen/epogen pi hcp english.pdf
Further reading
- Takeuchi M, Kobata A (1991). "Structures and functional roles of the sugar chains of human erythropoietins". Glycobiology 1 (4): 337–46. doi:10.1093/glycob/1.4.337. PMID 1820196.
- Semba RD, Juul SE (2002). "Erythropoietin in human milk: physiology and role in infant health". Journal of Human Lactation 18 (3): 252–61. doi:10.1177/089033440201800307. PMID 12192960.
- Ratcliffe PJ (2002). "From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway". Blood Purification 20 (5): 445–50. doi:10.1159/000065201. PMID 12207089.
- Westenfelder C (2002). "Unexpected renal actions of erythropoietin". Experimental Nephrology 10 (5-6): 294–8. doi:10.1159/000065304. PMID 12381912.
- Becerra SP, Amaral J (2002). "Erythropoietin--an endogenous retinal survival factor". The New England Journal of Medicine 347 (24): 1968–70. doi:10.1056/NEJMcibr022629. PMID 12477950.
- Genc S, Koroglu TF, Genc K (2004). "Erythropoietin and the nervous system". Brain Research 1000 (1-2): 19–31. doi:10.1016/j.brainres.2003.12.037. PMID 15053948.
- Fandrey J (2004). "Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 286 (6): R977–88. doi:10.1152/ajpregu.00577.2003. PMID 15142852.
- Juul S (2004). "Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models". Clinics in Perinatology 31 (1): 129–42. doi:10.1016/j.clp.2004.03.004. PMID 15183662.
- Buemi M, Caccamo C, Nostro L, Cavallaro E, Floccari F, Grasso G (2005). "Brain and cancer: the protective role of erythropoietin". Medicinal Research Reviews 25 (2): 245–59. doi:10.1002/med.20012. PMID 15389732.
- Sytkowski AJ (2007). "Does erythropoietin have a dark side? Epo signaling and cancer cells". Science's STKE 2007 (395): pe38. doi:10.1126/stke.3952007pe38. PMID 17636183.
- Goldwasser, Eugene (2011). A Bloody Long Journey: Erythropoietin and the Person Who Isolated It. Xlibris. ISBN 978-1-4568-5737-0.
External links
- NYT - 1987 announcement of Epogen's clinical success
- Dynepo EPAR (European Public Assessment Report), PDF format , credit European Medicines Agency
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Articles and topics related to Erythropoietin
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PDB gallery
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1buy: HUMAN ERYTHROPOIETIN, NMR MINIMIZED AVERAGE STRUCTURE
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1cn4: ERYTHROPOIETIN COMPLEXED WITH EXTRACELLULAR DOMAINS OF ERYTHROPOIETIN RECEPTOR
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1eer: CRYSTAL STRUCTURE OF HUMAN ERYTHROPOIETIN COMPLEXED TO ITS RECEPTOR AT 1.9 ANGSTROMS
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Hormones
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Endocrine
glands |
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Hypothalamic-
pituitary
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Hypothalamus
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- GnRH
- TRH
- Dopamine
- CRH
- GHRH
- Somatostatin (GHIH)
- MCH
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Posterior pituitary
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Anterior pituitary
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- FSH
- LH
- TSH
- Prolactin
- POMC
- CLIP
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- MSH
- Endorphins
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Adrenal axis
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- Adrenal cortex
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- cortisone
- DHEA
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- Adrenal medulla
- epinephrine
- norepinephrine
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Thyroid
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- Thyroid hormone
- Calcitonin
- Thyroid axis
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Parathyroid
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Gonadal axis
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Testis
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Ovary
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- estradiol
- progesterone
- activin and inhibin
- relaxin (pregnancy)
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Placenta
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- hCG
- HPL
- estrogen
- progesterone
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Pancreas
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- glucagon
- insulin
- amylin
- somatostatin
- pancreatic polypeptide
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Pineal gland
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- melatonin
- N,N-dimethyltryptamine
- 5-methoxy-N,N-dimethyltryptamine
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| Other |
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Thymus
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- Thymosins
- Thymosin α1
- Beta thymosins
- Thymopoietin
- Thymulin
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Digestive system
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Stomach
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Duodenum
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- CCK
- Incretins
- secretin
- motilin
- VIP
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Ileum
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- enteroglucagon
- peptide YY
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Liver/other
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- Insulin-like growth factor
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Adipose tissue
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- leptin
- adiponectin
- resistin
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Skeleton
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Kidney
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- JGA (renin)
- peritubular cells
- calcitriol
- prostaglandin
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Heart
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Physiology of the kidneys and acid-base physiology
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| Renal function |
| Secretion |
- clearance
- Pharmacokinetics
- Clearance of medications
- Urine flow rate
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| Reabsorption |
- Solvent drag
- sodium
- chloride
- urea
- glucose
- oligopeptides
- protein
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| Renal function |
- Glomerular filtration rate
- Creatinine clearance
- Renal clearance ratio
- Urea reduction ratio
- Kt/V
- Standardized Kt/V
- Measures of dialysis
- PAH clearance (Effective renal plasma flow
- Extraction ratio)
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| Filtration |
- Renal blood flow
- Ultrafiltration
- Countercurrent exchange
- Filtration fraction
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| Hormones |
- Antidiuretic hormone
- Aldosterone
- Atrial natriuretic peptide
- Renin
- Erythropoietin
- Calcitriol
- Prostaglandins
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| Acid-base balance |
- Fluid balance
- Darrow Yannet diagram
Body water: Intracellular fluid/Cytosol
- Extracellular fluid
- (Interstitial fluid
- Plasma
- Transcellular fluid)
- Base excess
- Davenport diagram
- Anion gap
- Arterial blood gas
- Winter's formula
- Buffering
- Bicarbonate buffer system
- Respiratory compensation
- Renal compensation
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| Other |
- Fractional sodium excretion
- BUN-to-creatinine ratio
- Tubuloglomerular feedback
- Natriuresis
- Urine
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Cytokines, glycoproteins: colony-stimulating factors
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| CFU-GEMM |
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| CFU-GM |
- Granulocyte macrophage colony-stimulating factor
- Granulocyte colony-stimulating factor
- Macrophage colony-stimulating factor
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| CFU-E |
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| CFU-Meg |
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Other hematological agents
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Antianemic
preparations
(B03) |
| Erythropoietins |
- Darbepoetin alfa
- Methoxy polyethylene glycol-epoetin beta
- Peginesatide
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| Iron supplements |
- Ferrous ascorbate
- Ferrous aspartate
- Ferrous carbonate
- Ferrous chloride
- Ferrous fumarate
- Ferrous gluconate
- Ferrous glycine sulfate
- Ferrous iodine
- Ferrous succinate
- Ferrous sulfate
- Ferrous tartrate
- Iron sucrose
- Sodium ferric gluconate complex
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Blood substitutes and
perfusion solutions (B05) |
- Dextran
- Gelatin agents
- Hemoglobin crosfumaril
- Hemoglobin raffimer
- Hydroxyethyl starch
- Icodextrin
- Mannitol
- Serum albumin
- Sorbitol
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| Enzymes (B06AA) |
- Bromelain
- Chymotrypsin
- Deoxyribonuclease
- Fibrinolysin
- Hyaluronidase
- Streptokinase
- Trypsin
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Drugs used i hereditary
angioedema (B06AC) |
- C1-inhibitor
- Conestat alfa
- Ecallantide
- Icatibant
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Growth factor receptor modulators
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| Angiopoietin |
- Agonists: Angiopoietin 1
- Angiopoietin 4
- Antagonists: Angiopoietin 2
- Angiopoietin 3
- Antibodies: Evinacumab (against angiopoietin 3)
- Nesvacumab (against angiopoietin 2)
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| CNTF |
- Agonists: Axokine
- CNTF
- Dapiclermin
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| EGF (ErbB) |
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EGF
(ErbB1/HER1)
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- Agonists: Amphiregulin
- Betacellulin
- EGF (urogastrone)
- Epigen
- Epiregulin
- Heparin-binding EGF-like growth factor (HB-EGF)
- Murodermin
- Nepidermin
- Transforming growth factor alpha (TGFα)
- Antibodies: Cetuximab
- Futuximab
- Imgatuzumab
- Matuzumab
- Necitumumab
- Nimotuzumab
- Panitumumab
- Zalutumumab
- Kinase inhibitors: Afatinib
- AG-490
- Brigatinib
- Canertinib
- Dacomitinib
- Erlotinib
- Gefitinib
- Grandinin
- Icotinib
- Lapatinib
- Neratinib
- Osimertinib
- Vandetanib
- WHI-P 154
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ErbB2/HER2
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- Antibodies: Ertumaxomab
- Pertuzumab
- Trastuzumab
- Trastuzumab emtansine
- Kinase inhibitors: Afatinib
- AG-490
- Lapatinib
- Mubritinib
- Neratinib
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ErbB3/HER3
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- Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C))
- Antibodies: Duligotumab
- Patritumab
- Seribantumab
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ErbB4/HER4
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- Agonists: Betacellulin
- Epigen
- Heparin-binding EGF-like growth factor (HB-EGF)
- Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))
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| FGF |
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FGFR1
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- Ersofermin
- FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20)
- Repifermin
- Trafermin
- Velafermin
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FGFR2
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- Ersofermin
- FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22)
- Palifermin
- Repifermin
- Sprifermin
- Trafermin
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FGFR3
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- Ersofermin
- FGF (1, 2 (bFGF), 4, 8, 9, 18, 23)
- Sprifermin
- Trafermin
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FGFR4
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- Ersofermin
- FGF (1, 2 (bFGF), 4, 6, 8, 9, 19)
- Trafermin
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Unsorted
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| HGF (c-Met) |
- Agonists: Hepatocyte growth factor
- Potentiators: Dihexa (PNB-0408)
- Antibodies: Emibetuzumab
- Ficlatuzumab
- Flanvotumab
- Onartuzumab
- Rilotumumab
- Kinase inhibitors: AM7 (drug)
- AMG-458
- Amuvatinib
- BMS-777607
- Cabozantinib
- Crizotinib
- Foretinib
- Golvatinib
- INCB28060
- JNJ-38877605
- K252a
- MK-2461
- PF-04217903
- PF-2341066
- PHA-665752
- SU-11274
- Tivantinib
- Volitinib
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| IGF |
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IGF-1
|
- Agonists: des(1-3)IGF-1
- Insulin-like growth factor-1 (somatomedin C)
- IGF-1 LR3
- Insulin-like growth factor-2 (somatomedin A)
- Insulin
- Mecasermin
- Mecasermin rinfabate
- Antibodies: AVE1642
- Cixutumumab
- Dalotuzumab
- Figitumumab
- Ganitumab
- Robatumumab
- R1507
- Teprotumumab
- Kinase inhibitors: Linsitinib
- NVP-ADW742
- NVP-AEW541
- OSl-906
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IGF-2
|
- Agonists: Insulin-like growth factor-2 (somatomedin A)
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Others
|
- Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7)
- Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
- Trofinetide
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| LNGF |
- Agonists: BDNF
- NGF
- NT-3
- NT-4
- Antibodies: Against NGF: Fasinumab
- Fulranumab
- Tanezumab
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| PDGF |
- Agonists: Becaplermin
- Platelet-derived growth factor (A, B, C, D)
- Antibodies: Olaratumab
- Ramucirumab
- Tovetumab
- Kinase inhibitors: Axitinib
- Crenolanib
- Imatinib
- Lenvatinib
- Masitinib
- Motesanib
- Nintedanib
- Pazopanib
- Radotinib
- Quizartinib
- Sunitinib
- Sorafenib
- Toceranib
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| RET (GFL) |
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GFRα1
|
- Agonists: Glial cell line-derived neurotrophic factor (GDNF)
- Liatermin
- Kinase inhibitors: Vandetanib
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GFRα2
|
- Agonists: Neurturin (NRTN)
- Kinase inhibitors: Vandetanib
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GFRα3
|
- Kinase inhibitors: Vandetanib
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GFRα4
|
- Agonists: Persephin (PSPN)
- Kinase inhibitors: Vandetanib
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| SCF (c-Kit) |
- Agonists: Ancestim
- Stem cell factor
- Kinase inhibitors: Axitinib
- Dasatinib
- Imatinib
- Masitinib
- Nilotinib
- Pazopanib
- Quizartinib
- Sorafenib
- Sunitinib
- Toceranib
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| TGFβ |
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| Trk |
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TrkA
|
- Agonists: Amitriptyline
- Gambogic amide
- NGF
- Tavilermide
- Kinase inhibitors: Entrectinib
- K252a
- Lestaurtinib
- LOXO-101
- Antibodies: Against NGF: Fasinumab
- Fulranumab
- Tanezumab
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TrkB
|
- Agonists: 3,7-DHF
- 3,7,8,2'-THF
- 4'-DMA-7,8-DHF
- 7,3'-DHF
- 7,8-DHF
- 7,8,2'-THF
- 7,8,3'-THF
- Amitriptyline
- BDNF
- Deoxygedunin
- Diosmetin
- HIOC
- LM22A-4
- N-Acetylserotonin
- NT-3
- NT-4
- Norwogonin (5,7,8-THF)
- R7
- TDP6
- Antagonists: ANA-12
- Cyclotraxin B
- Gossypetin (3,5,7,8,3',4'-HHF)
- Kinase inhibitors: Entrectinib
- K252a
- Lestaurtinib
- LOXO-101
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TrkC
|
- Kinase inhibitors: Entrectinib
- K252a
- Lestaurtinib
- LOXO-101
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| VEGF |
- Agonists: Placental growth factor (PGF)
- Telbermin
- VEGF (A, B, C, D (FIGF))
- Antibodies: Alacizumab pegol
- Bevacizumab
- Icrucumab
- Ramucirumab
- Ranibizumab
- Kinase inhibitors: Axitinib
- Cabozantinib
- Cediranib
- Lapatinib
- Lenvatinib
- Motesanib
- Nintedanib
- Pazopanib
- Pegaptanib
- Regorafenib
- Semaxanib
- Sorafenib
- Sunitinib
- Toceranib
- Tivozanib
- Vandetanib
- WHI-P 154
- Decoy receptors: Aflibercept
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| Others |
- Additional growth factors: Adrenomedullin
- Colony-stimulating factors (see here instead)
- Connective tissue growth factor (CTGF)
- Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
- Erythropoietin (see here instead)
- Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
- Glia maturation factor (GMF)
- Hepatoma-derived growth factor (HDGF)
- Interleukins/T-cell growth factors (see here instead)
- Leukemia inhibitory factor (LIF)
- Macrophage-stimulating protein (MSP; HLP, HGFLP)
- Midkine (NEGF2)
- Migration-stimulating factor (MSF; PRG4)
- Oncomodulin
- Pituitary adenylate cyclase-activating peptide (PACAP)
- Pleiotrophin
- Renalase
- Thrombopoietin (see here instead)
- Wnt signaling proteins
- Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
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- See also: Peptide receptor modulators
- Cytokine receptor modulators
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Cytokine receptor modulators
|
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| Chemokine |
|
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| CSF |
|
Erythropoietin
|
- Agonists: ARA-290
- Asialo erythropoietin
- Carbamylated erythropoietin
- CNTO-530
- Darbepoetin alfa
- Epoetin alfa
- Epoetin beta
- Epoetin delta
- Epoetin epsilon
- Epoetin gamma
- Epoetin kappa
- Epoetin omega
- Epoetin theta
- Epoetin zeta
- Erythropoietin (EPO)
- Erythropoietin-Fc
- Methoxy polyethylene glycol-epoetin beta (CERA/Mircera)
- Peginesatide
- Pegol sihematide (EPO-018B)
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G-CSF (CSF3)
|
- Agonists: Filgrastim
- Granulocyte colony-stimulating factor
- Lenograstim
- Leridistim
- Lipegfilgrastim
- Nartograstim
- Pegfilgrastim
- Pegnartograstim
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GM-CSF (CSF2)
|
- Agonists: Ecogramostim
- Granulocyte macrophage colony-stimulating factor
- Milodistim
- Molgramostim
- Regramostim
- Sargramostim
- Antibodies: Mavrilimumab
- MOR103
- Namilumab
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M-CSF (CSF1)
|
- Agonists: Cilmostim
- Interleukin-34
- Lanimostim
- Macrophage colony-stimulating factor
- Mirimostim
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SCF (c-Kit)
|
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Thrombopoietin
|
- Agonists: Eltrombopag
- Pegacaristim
- Promegapoietin
- Romiplostim
- Thrombopoietin (THPO, MGDF)
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| Interferon |
|
IFNAR (α/β, I)
|
- Agonists: Albinterferon
- Interferon alpha (interferon alfa, IFN-α)
- Interferon alfa (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21)
- Interferon alfa 2a
- Interferon alfa 2b
- Interferon alfa n1
- Interferon alfacon-1
- Interferon alpha-n3
- Interferon beta (IFN-β) (IFNB1, IFNB3)
- Interferon beta 1a
- Interferon beta 1b
- Interferon kappa (IFN-ε/κ/τ/ζ, IFNK)
- Interferon omega (IFN-ω, IFNW1)
- Peginterferon alfa-2a
- Peginterferon alfa-2b
- Antibodies: Anifrolumab
- Faralimomab
- MEDI-545
- Rontalizumab
- Sifalimumab
- Decoy receptors: Bifarcept
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IFNGR (γ, II)
|
- Agonists: Interferon gamma (IFN-γ)
- Interferon gamma 1b
|
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IFNLR (λ, III)
|
- See IL-28R (IFNLR) here instead.
|
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| Interleukin |
|
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| TGFβ |
|
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| TNF |
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| Others |
|
JAK
(inhibitors)
|
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JAK1
|
- Baricitinib
- CYT387
- Filgotinib
- Ruxolitinib
- Tofacitinib (tasocitinib, CP-690550)
- Upadacitinib
|
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JAK2
|
- AG-490
- Atiprimod
- AZD-1480
- Baricitinib
- CHZ868
- Cucurbitacin I (elatericin B, JSI-124)
- CYT387
- Lestaurtinib
- NSC-7908
- NSC-33994
- Pacritinib
- Ruxolitinib
- SD-1008
- Tofacitinib (tasocitinib, CP-690550)
|
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JAK3
|
- AG-490
- Cercosporamide
- TCS-21311
- Tofacitinib (tasocitinib, CP-690550)
- WHI-P 154
- ZM-39923
- ZM-449829
|
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Others
|
- Additional cytokines: FMS-like tyrosine kinase 3 ligand (FLT3L)
- Leukemia inhibitory factor (LIF)
- Oncostatin M (OSM)
- Thymic stromal lymphopoietin (TSLP)
- Additional cytokine receptor modulators: Emfilermin
- Lestaurtinib
- Midostaurin
- Quizartinib
- Sorafenib
- Sunitinib
|
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- See also: Peptide receptor modulators
- Growth factor receptor modulators
|
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