| HGF |
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| Available structures |
| PDB |
Ortholog search: PDBe RCSB |
| List of PDB id codes |
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1BHT, 1GMN, 1GMO, 1GP9, 1NK1, 1SHY, 1SI5, 2HGF, 2QJ2, 3HMS, 3HMT, 3HN4, 3MKP, 3SP8, 4K3J, 4O3T, 4O3U, 5COE, 5CP9, 5CS1, 5CS3, 5CS5, 5CS9, 5CSQ, 5CT1, 5CT2, 5CT3, 4D3C
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| Identifiers |
| Aliases |
HGF, DFNB39, F-TCF, HGFB, HPTA, SF, hepatocyte growth factor |
| External IDs |
OMIM: 142409 MGI: 96079 HomoloGene: 503 GeneCards: HGF |
| Gene ontology |
| Molecular function |
• protein binding
• identical protein binding
• chemoattractant activity
• protein heterodimerization activity
• growth factor activity
• serine-type endopeptidase activity
• protein tyrosine kinase activity
• Ras guanyl-nucleotide exchange factor activity
• phosphatidylinositol-4,5-bisphosphate 3-kinase activity
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| Cellular component |
• membrane
• extracellular region
• platelet alpha granule lumen
• extracellular space
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| Biological process |
• negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
• mitotic nuclear division
• negative regulation of hydrogen peroxide-mediated programmed cell death
• positive regulation of neuron projection regeneration
• positive regulation of interleukin-10 production
• positive regulation of cell migration
• cellular response to hepatocyte growth factor stimulus
• negative regulation of release of cytochrome c from mitochondria
• negative regulation of interleukin-6 production
• platelet degranulation
• negative regulation of apoptotic process
• regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling
• positive regulation of angiogenesis
• positive regulation of myelination
• positive regulation of osteoblast differentiation
• activation of MAPK activity
• myoblast proliferation
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• animal organ regeneration
• cell morphogenesis
• positive regulation of cell proliferation
• hyaluronan metabolic process
• positive regulation of DNA biosynthetic process
• negative regulation of peptidyl-serine phosphorylation
• epithelial to mesenchymal transition
• positive regulation of peptidyl-tyrosine phosphorylation
• cell chemotaxis
• liver development
• positive regulation of phosphatidylinositol 3-kinase signaling
• regulation of p38MAPK cascade
• cell proliferation
• negative regulation of autophagy
• hepatocyte growth factor receptor signaling pathway
• negative regulation of inflammatory response
• positive regulation of transcription from RNA polymerase II promoter
• regulation of tau-protein kinase activity
• proteolysis
• positive chemotaxis
• MAPK cascade
• regulation of phosphatidylinositol 3-kinase signaling
• peptidyl-tyrosine phosphorylation
• positive regulation of GTPase activity
• phosphatidylinositol phosphorylation
• phosphatidylinositol-mediated signaling
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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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NM_000601
NM_001010931
NM_001010932
NM_001010933
NM_001010934
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NM_010427
NM_001289458
NM_001289459
NM_001289460
NM_001289461
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| RefSeq (protein) |
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NP_000592
NP_001010931
NP_001010932
NP_001010933
NP_001010934
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NP_001276387.1
NP_001276388.1
NP_001276389.1
NP_001276390.1
NP_034557.3
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| Location (UCSC) |
Chr 7: 81.7 – 81.77 Mb |
Chr 5: 16.55 – 16.62 Mb |
| PubMed search |
[1] |
[2] |
| Wikidata |
| View/Edit Human |
View/Edit Mouse |
Hepatocyte growth factor (HGF) (or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells and T cells. It has been shown to have a major role in embryonic organ development, specifically in myogenesis, in adult organ regeneration, and in wound healing.[3]
Contents
- 1 Function
- 2 Structure
- 3 Clinical significance
- 3.1 Circulating plasma levels
- 4 Pharmacokinetics
- 5 Modulators
- 6 Interactions
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
Function
Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor.[4][5] Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration.[6]
Structure
It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta-chain. A disulfide bond between the alpha and beta chains produces the active, heterodimeric molecule. The protein belongs to the plasminogen subfamily of S1 peptidases but has no detectable protease activity.[6]
Clinical significance
Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[7][8] As well as the well-characterised effects of HGF on epithelial cells, endothelial cells and haemopoietic progenitor cells, HGF also regulates the chemotaxis of T cells into heart tissue. Binding of HGF by c-Met, expressed on T cells, causes the upregulation of c-Met, CXCR3, and CCR4 which in turn imbues them with the ability to migrate into heart tissue.[9]
HGF may further play a role as an indicator for prognosis of chronicity for Chikungunya virus induced arthralgia. High HGF levels correlate with high rates of recovery.[10]
Excessive local expression of HGF in the breasts has been implicated in macromastia.[11] HGF is also importantly involved in normal mammary gland development.[12][13]
HGF has been implicated in a variety of cancers, including of the lungs, pancreas, thyroid, colon, and breast.[14][15][16]
Circulating plasma levels
Plasma from patients with advanced heart failure presents increased levels of HGF, which correlates with a negative prognosis and a high risk of mortality.[17][18] Circulating HGF has been also identified as a prognostic marker of severity in patients suffering from hypertension.[19][20] Circulating HGF has been also suggested as a precocious biomarker for the acute phase of bowel inflammation.[21]
Pharmacokinetics
Exogenous HGF administered by intravenous injection is cleared rapidly from circulation by the liver, with a half-life of approximately 4 minutes.[22][23][24][25]
Modulators
Dihexa is an orally active, centrally penetrant small-molecule compound that directly binds to HGF and potentiates its ability to activate its receptor, c-Met.[26] It is a strong inducer of neurogenesis and is being studied for the potential treatment of Alzheimer's disease and Parkinson's disease.[27][28]
Interactions
Hepatocyte growth factor has been shown to interact with the protein product of the c-Met oncogene, identified as the HGF receptor (HGFR).[4][29][30] Both overexpression of the Met/HGFR receptor protein and autocrine activation of Met/HGFR by simultaneous expression of the hepatocyte growth factor ligand have been implicated in oncogenesis.[31][32] Hepatocyte growth factor interacts with the sulfated glycosaminoglycans heparan sulfate and dermatan sulfate.[33][34] The interaction with heparan suflate allows hepatocyte growth factor to form a complex with c-Met that is able to transduce intracellular signals leading to cell division and cell migration.[33][35]
See also
- Epidermal growth factor
- Insulin-like growth factor 1
References
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
- ^ a b Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (February 1991). "Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product". Science. 251 (4995): 802–4. doi:10.1126/science.1846706. PMID 1846706.
- ^ Johnson M, Koukoulis G, Matsumoto K, Nakamura T, Iyer A (June 1993). "Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells". Hepatology. 17 (6): 1052–61. doi:10.1016/0270-9139(93)90122-4. PMID 8514254.
- ^ a b "Entrez Gene: HGF hepatocyte growth factor (hepapoietin A; scatter factor)".
- ^ Yang ZJ, Zhang YR, Chen B, Zhang SL, Jia EZ, Wang LS, Zhu TB, Li CJ, Wang H, Huang J, Cao KJ, Ma WZ, Wu B, Wang LS, Wu CT (July 2009). "Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease". Molecular Biology Reports. 36 (6): 1323–9. doi:10.1007/s11033-008-9315-3. PMID 18649012.
- ^ Hahn W, Pyun WB, Kim DS, Yoo WS, Lee SD, Won JH, Shin GJ, Kim JM, Kim S (October 2011). "Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model". The Journal of Gene Medicine. 13 (10): 549–55. doi:10.1002/jgm.1603. PMID 21898720.
- ^ Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, Cooper D, Nadkarni S, Fu H, Steinbruchel DA, Pitzalis C, Anderson G, Bucy P, Lombardi G, Breckenridge R, Marelli-Berg FM (June 2015). "Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release". Immunity. 42 (6): 1087–99. doi:10.1016/j.immuni.2015.05.014. PMC 4510150. PMID 26070483.
- ^ Chow A, Her Z, Ong EK, Chen JM, Dimatatac F, Kwek DJ, Barkham T, Yang H, Rénia L, Leo YS, Ng LF (January 2011). "Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor". The Journal of Infectious Diseases. 203 (2): 149–57. doi:10.1093/infdis/jiq042. PMC 3071069. PMID 21288813.
- ^ Zhong A, Wang G, Yang J, Xu Q, Yuan Q, Yang Y, Xia Y, Guo K, Horch RE, Sun J (July 2014). "Stromal-epithelial cell interactions and alteration of branching morphogenesis in macromastic mammary glands". Journal of Cellular and Molecular Medicine. 18 (7): 1257–66. doi:10.1111/jcmm.12275. PMID 24720804.
- ^ Niranjan B, Buluwela L, Yant J, Perusinghe N, Atherton A, Phippard D, et al. (1995). "HGF/SF: a potent cytokine for mammary growth, morphogenesis and development". Development. 121 (9): 2897–908. PMID 7555716.
- ^ Kamalati T, Niranjan B, Yant J, Buluwela L (1999). "HGF/SF in mammary epithelial growth and morphogenesis: in vitro and in vivo models". J Mammary Gland Biol Neoplasia. 4 (1): 69–77. PMID 10219907.
- ^ Thomas R. Ziegler; Glenn F. Pierce; David N. Herndon (6 December 2012). Growth Factors and Wound Healing: Basic Science and Potential Clinical Applications. Springer Science & Business Media. pp. 311–. ISBN 978-1-4612-1876-0.
- ^ Sheen-Chen SM, Liu YW, Eng HL, Chou FF (March 2005). "Serum levels of hepatocyte growth factor in patients with breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 14 (3): 715–7. doi:10.1158/1055-9965.EPI-04-0340. PMID 15767355.
- ^ El-Attar HA, Sheta MI (2011). "Hepatocyte growth factor profile with breast cancer". Indian Journal of Pathology & Microbiology. 54 (3): 509–13. doi:10.4103/0377-4929.85083. PMID 21934211.
- ^ Richter B, Koller L, Hohensinner PJ, Zorn G, Brekalo M, Berger R, Mörtl D, Maurer G, Pacher R, Huber K, Wojta J, Hülsmann M, Niessner A (September 2013). "A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure". International Journal of Cardiology. 168 (2): 1251–7. doi:10.1016/j.ijcard.2012.11.052. PMID 23218577.
- ^ Rychli K, Richter B, Hohensinner PJ, Kariem Mahdy A, Neuhold S, Zorn G, Berger R, Mörtl D, Huber K, Pacher R, Wojta J, Niessner A, Hülsmann M (July 2011). "Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure". Heart. 97 (14): 1158–63. doi:10.1136/hrt.2010.220228. PMID 21572126.
- ^ Nakamura S, Morishita R, Moriguchi A, Yo Y, Nakamura Y, Hayashi S, Matsumoto K, Matsumoto K, Nakamura T, Higaki J, Ogihara T (December 1998). "Hepatocyte growth factor as a potential index of complication in diabetes mellitus". Journal of Hypertension. 16 (12 Pt 2): 2019–26. doi:10.1291/hypres.22.161. PMID 9886892.
- ^ Nakamura S, Morishita R, Moriguchi A, Yo Y, Nakamura Y, Hayashi S, Matsumoto K, Matsumoto K, Nakamura T, Higaki J, Ogihara T (December 1998). "Hepatocyte growth factor as a potential index of complication in diabetes mellitus". Journal of Hypertension. 16 (12 Pt 2): 2019–26. doi:10.1291/hypres.22.161. PMID 9886892.
- ^ Sorour AE, Lönn J, Nakka SS, Nayeri T, Nayeri F (January 2015). "Evaluation of hepatocyte growth factor as a local acute phase response marker in the bowel: the clinical impact of a rapid diagnostic test for immediate identification of acute bowel inflammation". Cytokine. 71 (1): 8–15. doi:10.1016/j.cyto.2014.07.255. PMID 25174881.
- ^ Yang J, Chen S, Huang L, Michalopoulos GK, Liu Y (April 2001). "Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth". Hepatology. 33 (4): 848–59. doi:10.1053/jhep.2001.23438. PMC 1821076. PMID 11283849.
- ^ Appasamy R, Tanabe M, Murase N, Zarnegar R, Venkataramanan R, Van Thiel DH, Michalopoulos GK (March 1993). "Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats". Laboratory Investigation; A Journal of Technical Methods and Pathology. 68 (3): 270–6. PMID 8450646.
- ^ Kato Y, Liu KX, Nakamura T, Sugiyama Y (August 1994). "Heparin-hepatocyte growth factor complex with low plasma clearance and retained hepatocyte proliferating activity". Hepatology. 20 (2): 417–24. doi:10.1002/hep.1840200223. PMID 8045504.
- ^ Yu Y, Yao AH, Chen N, Pu LY, Fan Y, Lv L, Sun BC, Li GQ, Wang XH (July 2007). "Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration". Molecular Therapy. 15 (7): 1382–9. doi:10.1038/sj.mt.6300202. PMID 17519892.
- ^ Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW (November 2014). "The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system". The Journal of Pharmacology and Experimental Therapeutics. 351 (2): 390–402. doi:10.1124/jpet.114.218735. PMC 4201273. PMID 25187433.
- ^ Wright JW, Harding JW (2015). "The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease". Journal of Alzheimer's Disease. 45 (4): 985–1000. doi:10.3233/JAD-142814. PMID 25649658.
- ^ Wright JW, Kawas LH, Harding JW (February 2015). "The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases". Progress in Neurobiology. 125: 26–46. doi:10.1016/j.pneurobio.2014.11.004. PMID 25455861.
- ^ Comoglio PM (1993). "Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells". Exs. 65: 131–65. PMID 8380735.
- ^ Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan RP, Hartmann G, Zarnegar R, Michalopoulos GK (October 1991). "Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor". The EMBO Journal. 10 (10): 2867–78. PMC 452997. PMID 1655405.
- ^ Johnson M, Koukoulis G, Kochhar K, Kubo C, Nakamura T, Iyer A (September 1995). "Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection". Cancer Letters. 96 (1): 37–48. doi:10.1016/0304-3835(95)03915-j. PMID 7553606.
- ^ Kochhar KS, Johnson ME, Volpert O, Iyer AP (1995). "Evidence for autocrine basis of transformation in NIH-3T3 cells transfected with met/HGF receptor gene". Growth Factors. 12 (4): 303–13. doi:10.3109/08977199509028968. PMID 8930021.
- ^ a b Lyon M, Deakin JA, Gallagher JT (January 2002). "The mode of action of heparan and dermatan sulfates in the regulation of hepatocyte growth factor/scatter factor". The Journal of Biological Chemistry. 277 (2): 1040–6. doi:10.1074/jbc.M107506200. PMID 11689562.
- ^ Lyon M, Deakin JA, Rahmoune H, Fernig DG, Nakamura T, Gallagher JT (Jan 1998). "Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate". J Biol Chem. 273 (1): 271–8. doi:10.1074/jbc.273.1.271. PMID 9417075.
- ^ Sergeant N, Lyon M, Rudland PS, Fernig DG, Delehedde M (June 2000). "Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44". The Journal of Biological Chemistry. 275 (22): 17094–9. doi:10.1074/jbc.M000237200. PMID 10747885.
Further reading
- Michalopoulos GK, Zarnegar R (1992). "Hepatocyte Growth Factor". Hepatology. 15 (1): 149–54. doi:10.1002/hep.1840150125.
- Nakamura T (1992). "Structure and function of hepatocyte growth factor". Progress in Growth Factor Research. 3 (1): 67–85. doi:10.1016/0955-2235(91)90014-U. PMID 1838014.
- Ware LB, Matthay MA (May 2002). "Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair". American Journal of Physiology. Lung Cellular and Molecular Physiology. 282 (5): L924–40. doi:10.1152/ajplung.00439.2001. PMID 11943656.
- Funakoshi H, Nakamura T (January 2003). "Hepatocyte growth factor: from diagnosis to clinical applications". Clinica Chimica Acta; International Journal of Clinical Chemistry. 327 (1-2): 1–23. doi:10.1016/S0009-8981(02)00302-9. PMID 12482615.
- Skibinski G (2004). "The role of hepatocyte growth factor/c-met interactions in the immune system". Archivum Immunologiae Et Therapiae Experimentalis. 51 (5): 277–82. PMID 14626426.
- Kalluri R, Neilson EG (December 2003). "Epithelial-mesenchymal transition and its implications for fibrosis". The Journal of Clinical Investigation. 112 (12): 1776–84. doi:10.1172/JCI20530. PMC 297008. PMID 14679171.
- Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG (October 2005). "Hepatocyte growth factor/scatter factor and prostate cancer: a review". Histology and Histopathology. 20 (4): 1339–49. PMID 16136515.
- Kemp LE, Mulloy B, Gherardi E (June 2006). "Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors". Biochemical Society Transactions. 34 (Pt 3): 414–7. doi:10.1042/BST0340414. PMID 16709175.
External links
- Hepatocyte growth factor at the US National Library of Medicine Medical Subject Headings (MeSH)
- Hepatocyte growth factor on the Atlas of Genetics and Oncology
- UCSD Signaling Gateway Molecule Page on HGF
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PDB gallery
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1bht: NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR
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1gmn: CRYSTAL STRUCTURES OF NK1-HEPARIN COMPLEXES REVEAL THE BASIS FOR NK1 ACTIVITY AND ENABLE ENGINEERING OF POTENT AGONISTS OF THE MET RECEPTOR
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1gmo: CRYSTAL STRUCTURES OF NK1-HEPARIN COMPLEXES REVEAL THE BASIS FOR NK1 ACTIVITY AND ENABLE ENGINEERING OF POTENT AGONISTS OF THE MET RECEPTOR
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1gp9: A NEW CRYSTAL FORM OF THE NK1 SPLICE VARIANT OF HGF/SF DEMONSTRATES EXTENSIVE HINGE MOVEMENT AND SUGGESTS THAT THE NK1 DIMER ORIGINATES BY DOMAIN SWAPPING
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1nk1: NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR (HGF/SF) AT 2.5 ANGSTROM RESOLUTION
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1shy: The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.
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1si5: Protease-like domain from 2-chain hepatocyte growth factor
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2hgf: HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
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Intercellular signaling peptides and proteins / ligands
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| Growth factors |
- Epidermal growth factor
- Fibroblast growth factor
- Nerve growth factor
- Platelet-derived growth factor
- Transforming growth factor beta superfamily
- Vascular endothelial growth factor
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| Ephrin |
- EFNA1
- EFNA2
- EFNA3
- EFNA4
- EFNA5
- EFNB1
- EFNB2
- EFNB3
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| Other |
- Adipokine
- Agouti signaling protein
- Agouti-related protein
- Angiogenic protein
- CCN intercellular signaling protein
- Cysteine-rich protein 61
- Connective tissue growth factor
- Nephroblastoma overexpressed protein
- Cytokine
- Endothelin
- Hedgehog protein
- Interferon
- Kinin
- Parathyroid hormone-related protein
- Semaphorin
- Somatomedin
- Tolloid-like metalloproteinase
- Tumor necrosis factor
- Wnt protein
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see also extracellular ligand disorders
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Growth factors
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| Fibroblast |
| FGF receptor ligands: |
- FGF1/FGF2/FGF5
- FGF3/FGF4/FGF6
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| KGF |
- FGF7/FGF10/FGF22
- FGF8/FGF17/FGF18
- FGF9/FGF16/FGF20
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| FGF homologous factors: |
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| hormone-like: |
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| EGF-like domain |
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| TGFβ pathway |
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| Insulin-like |
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| Platelet-derived |
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| Vascular endothelial |
- VEGF-A
- VEGF-B
- VEGF-C
- VEGF-D
- PGF
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| Other |
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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
- Depatuxizumab
- Depatuxizumab mafodotin
- Futuximab
- Imgatuzumab
- Matuzumab
- Necitumumab
- Nimotuzumab
- Panitumumab
- Zalutumumab
- Kinase inhibitors: Afatinib
- AG-490
- Agerafenib
- 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 duocarmazine
- 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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- Agonists: 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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- Agonists: Ersofermin
- FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22)
- Palifermin
- Repifermin
- Sprifermin
- Trafermin
- Antibodies: Aprutumab
- Aprutumab ixadotin
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FGFR3
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- Agonists: Ersofermin
- FGF (1, 2 (bFGF), 4, 8, 9, 18, 23)
- Sprifermin
- Trafermin
- Antibodies: Burosumab (against FGF23)
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FGFR4
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- Agonists: 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
- Telisotuzumab
- Telisotuzumab vedotin
- 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
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- 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
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- Agonists: Insulin-like growth factor-2 (somatomedin A)
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Others
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- 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
- Cenegermin
- NGF
- NT-3
- NT-4
- Antibodies: Against NGF: Fasinumab
- Fulranumab
- Ranevetmab
- Tanezumab
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| PDGF |
- Agonists: Becaplermin
- Platelet-derived growth factor (A, B, C, D)
- Antibodies: Olaratumab
- Ramucirumab
- Tovetumab
- Kinase inhibitors: Agerafenib
- Axitinib
- Crenolanib
- Imatinib
- Lenvatinib
- Masitinib
- Motesanib
- Nintedanib
- Pazopanib
- Radotinib
- Quizartinib
- Sunitinib
- Sorafenib
- Toceranib
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| RET (GFL) |
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GFRα1
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- Agonists: Glial cell line-derived neurotrophic factor (GDNF)
- Liatermin
- Kinase inhibitors: Vandetanib
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GFRα2
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- Agonists: Neurturin (NRTN)
- Kinase inhibitors: Vandetanib
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GFRα3
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- Kinase inhibitors: Vandetanib
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GFRα4
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- Agonists: Persephin (PSPN)
- Kinase inhibitors: Vandetanib
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Unsorted
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- Kinase inhibitors: Agerafenib
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| SCF (c-Kit) |
- Agonists: Ancestim
- Stem cell factor
- Kinase inhibitors: Agerafenib
- 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
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- Agonists: Amitriptyline
- Cenegermin
- Gambogic amide
- NGF
- Tavilermide
- Kinase inhibitors: Entrectinib
- K252a
- Lestaurtinib
- LOXO-101
- Antibodies: Against NGF: Fasinumab
- Fulranumab
- Ranevetmab
- Tanezumab
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TrkB
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- 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
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- Kinase inhibitors: Entrectinib
- K252a
- Lestaurtinib
- LOXO-101
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| VEGF |
- Agonists: Placental growth factor (PGF)
- Telbermin
- VEGF (A, B, C, D (FIGF))
- Allosteric modulators: Cyclotraxin B
- Antibodies: Alacizumab pegol
- Bevacizumab
- Icrucumab
- Ramucirumab
- Ranibizumab
- Kinase inhibitors: Agerafenib
- 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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