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Ephrin - Wikipedia

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id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Family of proteins</div> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox"><tbody><tr><th colspan="2" class="infobox-above">Ephrin</th></tr><tr><td colspan="2" class="infobox-image"><span class="mw-default-size" typeof="mw:File/Frameless"><a href="/wiki/File:PDB_2hle_EBI.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/8/85/PDB_2hle_EBI.jpg/220px-PDB_2hle_EBI.jpg" decoding="async" width="220" height="165" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/85/PDB_2hle_EBI.jpg/330px-PDB_2hle_EBI.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/8/85/PDB_2hle_EBI.jpg/440px-PDB_2hle_EBI.jpg 2x" data-file-width="800" data-file-height="600" /></a></span><div class="infobox-caption">Ectodomains of the Ephb4-Ephrinb2 protein complex</div></td></tr><tr><th colspan="2" class="infobox-header" style="background-color: #ddd">Identifiers</th></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3">Symbol</th><td class="infobox-data" style="background-color: #eee">Ephrin</td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/Pfam" title="Pfam">Pfam</a></th><td class="infobox-data pfam" style="background-color: #eee"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/interpro/entry/pfam/PF00812">PF00812</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/Pfam" title="Pfam">Pfam</a> clan</th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/interpro/set/pfam/CL0026/">CL0026</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/InterPro" title="InterPro">InterPro</a></th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/interpro/entry/IPR001799">IPR001799</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/PROSITE" title="PROSITE">PROSITE</a></th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="https://prosite.expasy.org/PDOC01003">PDOC01003</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/Structural_Classification_of_Proteins" class="mw-redirect" title="Structural Classification of Proteins">SCOP2</a></th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="http://scop2.mrc-lmb.cam.ac.uk/search?t=txt;q=1kgy">1kgy</a> / <a rel="nofollow" class="external text" href="https://scop.berkeley.edu/pdb/code=1kgy">SCOPe</a> / <a rel="nofollow" class="external text" href="http://supfam.org/SUPERFAMILY/cgi-bin/search.cgi?search_field=1kgy">SUPFAM</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/Conserved_Domain_Database" title="Conserved Domain Database">CDD</a></th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd02675">cd02675</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3"><a href="/wiki/Membranome_database" title="Membranome database">Membranome</a></th><td class="infobox-data" style="background-color: #eee"><a rel="nofollow" class="external text" href="http://membranome.org/protein_superfamilies/70">70</a></td></tr><tr><td colspan="2" class="infobox-full-data" style="background-color: #eee"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1257001546"><table class="infobox mw-collapsible mw-collapsed" style="float:none; clear:none; margin:0; border-width:0; border-collapse:collapse; text-align:left; width:100%"><tbody><tr><th colspan="2" class="infobox-header" style="background-color: #ddd">Available protein structures:</th></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3; border:#fafafa 2px solid; border-width:3px 2px 0 0;"><a href="/wiki/Pfam" title="Pfam">Pfam</a> &#160;</th><td class="infobox-data" style="background-color: #eee; border:#fafafa 2px solid; border-width:3px 0 0 2px;"><a rel="nofollow" class="external text" href="http://pfam.xfam.org/family/PF00812?tab=pdbBlock">structures</a> / <a rel="nofollow" class="external text" href="http://prodata.swmed.edu/ecod/complete/search?kw=PF00812">ECOD</a> &#160;</td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3; border:#fafafa 2px solid; border-width:3px 2px 0 0;"><a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a></th><td class="infobox-data" style="background-color: #eee; border:#fafafa 2px solid; border-width:3px 0 0 2px;"><a rel="nofollow" class="external text" href="https://www.rcsb.org/search?q=rcsb_polymer_entity_annotation.annotation_id:PF00812%20AND%20rcsb_polymer_entity_annotation.type:Pfam">RCSB PDB</a>; <a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/entry/search/index?pfam_accession:PF00812">PDBe</a>; <a rel="nofollow" class="external text" href="https://pdbj.org/search/pdb?other_db_select=PFam&amp;other_db_field=PF00812">PDBj</a></td></tr><tr><th scope="row" class="infobox-label" style="background-color: #e7dcc3; border:#fafafa 2px solid; border-width:3px 2px 0 0;"><a href="/wiki/PDBsum" title="PDBsum">PDBsum</a></th><td class="infobox-data" style="background-color: #eee; border:#fafafa 2px solid; border-width:3px 0 0 2px;"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPfamStr.pl?pfam_id=PF00812">structure summary</a></td></tr></tbody></table></td></tr></tbody></table> <p><b>Ephrins</b> (also known as <b>ephrin ligands</b> or <b>Eph family receptor interacting proteins</b>) are <a href="/wiki/Protein_family" title="Protein family">a family of proteins</a> that serve as the <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a> of the <a href="/wiki/Eph_receptor" class="mw-redirect" title="Eph receptor">Eph receptor</a>. Eph receptors in turn compose the largest known subfamily of <a href="/wiki/Receptor_protein-tyrosine_kinases" class="mw-redirect" title="Receptor protein-tyrosine kinases">receptor protein-tyrosine kinases</a> (RTKs). </p><p>Since ephrin ligands (ephrins) and Eph receptors (Ephs) are both <a href="/wiki/Membrane_protein" title="Membrane protein">membrane-bound proteins</a>, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct <a href="/wiki/Cell%E2%80%93cell_interaction" title="Cell–cell interaction">cell–cell interaction</a>. Eph/ephrin signaling regulates a variety of biological processes during <a href="/wiki/Embryogenesis" class="mw-redirect" title="Embryogenesis">embryonic development</a> including the <a href="/wiki/Axon_guidance" title="Axon guidance">guidance of axon growth cones</a>,<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">&#91;</span>1<span class="cite-bracket">&#93;</span></a></sup> formation of tissue boundaries,<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">&#91;</span>2<span class="cite-bracket">&#93;</span></a></sup> <a href="/wiki/Cell_migration" title="Cell migration">cell migration</a>, and <a href="/wiki/Segmentation_(biology)" title="Segmentation (biology)">segmentation</a>.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">&#91;</span>3<span class="cite-bracket">&#93;</span></a></sup> Additionally, Eph/ephrin signaling has been identified to play a critical role in the maintenance of several processes during adulthood including <a href="/wiki/Long-term_potentiation" title="Long-term potentiation">long-term potentiation</a>,<sup id="cite_ref-pmid12094214_4-0" class="reference"><a href="#cite_note-pmid12094214-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> <a href="/wiki/Angiogenesis" title="Angiogenesis">angiogenesis</a>,<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">&#91;</span>5<span class="cite-bracket">&#93;</span></a></sup> and <a href="/wiki/Stem_cell" title="Stem cell">stem cell</a> differentiation.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">&#91;</span>6<span class="cite-bracket">&#93;</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Classification">Classification</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=1" title="Edit section: Classification"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Ephrin ligands are divided into two subclasses of ephrin-A and ephrin-B based on their structure and linkage to the cell membrane. Ephrin-As are anchored to the membrane by a <a href="/wiki/Glycosylphosphatidylinositol" title="Glycosylphosphatidylinositol">glycosylphosphatidylinositol</a> (GPI) linkage and lack a cytoplasmic domain, while ephrin-Bs are attached to the membrane by a single transmembrane domain that contains a short cytoplasmic <a href="/wiki/PDZ_domain" title="PDZ domain">PDZ-binding</a> motif. The genes that encode the ephrin-A and ephrin-B proteins are designated as <i>EFNA</i> and <i>EFNB</i> respectively. Eph receptors in turn are classified as either EphAs or EphBs based on their <a href="/wiki/Dissociation_constant" title="Dissociation constant">binding affinity</a> for either the ephrin-A or ephrin-B ligands.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">&#91;</span>7<span class="cite-bracket">&#93;</span></a></sup> </p><p>Of the eight ephrins that have been identified in humans there are five known ephrin-A ligands (ephrin-A1-5) that interact with nine EphAs (EphA1-8 and EphA10) and three ephrin-B ligands (ephrin-B1-3) that interact with five EphBs (EphB1-4 and EphB6).<sup id="cite_ref-pmid12094214_4-1" class="reference"><a href="#cite_note-pmid12094214-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">&#91;</span>8<span class="cite-bracket">&#93;</span></a></sup> Ephs of a particular subclass demonstrate an ability to bind with high affinity to all ephrins of the corresponding subclass, but in general have little to no cross-binding to ephrins of the opposing subclass.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">&#91;</span>9<span class="cite-bracket">&#93;</span></a></sup> However, there are a few exceptions to this intrasubclass binding specificity as it has recently been shown that <a href="/wiki/EFNB3" class="mw-redirect" title="EFNB3">ephrin-B3</a> is able to bind to and activate <a href="/wiki/EPHA4" class="mw-redirect" title="EPHA4">EPH receptor A4</a> and <a href="/wiki/EFNA5" class="mw-redirect" title="EFNA5">ephrin-A5</a> can bind to and activate <a href="/wiki/EPHB2" class="mw-redirect" title="EPHB2">Eph receptor B2</a>.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">&#91;</span>10<span class="cite-bracket">&#93;</span></a></sup> EphAs/ephrin-As typically bind with high affinity, which can partially be attributed to the fact that ephrinAs interact with EphAs by a "lock-and-key" mechanism that requires little <a href="/wiki/Conformational_change" title="Conformational change">conformational change</a> of the EphAs upon ligand binding. In contrast EphBs typically bind with lower affinity than EphAs/ephring-As since they utilize an "induced fit" mechanism that requires a greater conformational change of EphBs to bind ephrin-Bs.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">&#91;</span>11<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Function">Function</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=2" title="Edit section: Function"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Axon_guidance">Axon guidance</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=3" title="Edit section: Axon guidance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>During the development of the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a> Eph/ephrin signaling plays a critical role in the cell–cell mediated migration of several types of neuronal <a href="/wiki/Axon" title="Axon">axons</a> to their target destinations. Eph/ephrin signaling controls the guidance of neuronal axons through their ability to inhibit the survival of axonal <a href="/wiki/Growth_cone" title="Growth cone">growth cones</a>, which repels the migrating axon away from the site of Eph/ephrin activation.<sup id="cite_ref-Marquadt_12-0" class="reference"><a href="#cite_note-Marquadt-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup> The growth cones of migrating axons do not simply respond to absolute levels of Ephs or ephrins in cells that they contact, but rather respond to relative levels of Eph and ephrin expression,<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">&#91;</span>13<span class="cite-bracket">&#93;</span></a></sup> which allows migrating axons that express either Ephs or ephrins to be directed along gradients of Eph or ephrin expressing cells towards a destination where axonal growth cone survival is no longer completely inhibited.<sup id="cite_ref-Marquadt_12-1" class="reference"><a href="#cite_note-Marquadt-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup> </p><p>Although Eph-ephrin activation is usually associated with decreased growth cone survival and the repulsion of migrating axons, it has recently been demonstrated that growth cone survival does not depend just on Eph-ephrin activation, but rather on the differential effects of "forward" signaling by the Eph receptor or "reverse" signaling by the ephrin ligand on growth cone survival.<sup id="cite_ref-Marquadt_12-2" class="reference"><a href="#cite_note-Marquadt-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-Petros_14-0" class="reference"><a href="#cite_note-Petros-14"><span class="cite-bracket">&#91;</span>14<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Retinotopic_mapping">Retinotopic mapping</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=4" title="Edit section: Retinotopic mapping"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The formation of an organized <a href="/wiki/Retinotopy" title="Retinotopy">retinotopic</a> map in the <a href="/wiki/Superior_colliculus" title="Superior colliculus">superior colliculus</a> (SC) (referred to as the optic tectum in lower vertebrates) requires the proper migration of the axons of <a href="/wiki/Retinal_ganglion_cell" title="Retinal ganglion cell">retinal ganglion cells</a> (RGCs) from the retina to specific regions in the SC that is mediated by gradients of Eph and ephrin expression in both the SC and in migrating RGCs leaving the retina.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">&#91;</span>15<span class="cite-bracket">&#93;</span></a></sup> The decreased survival of axonal growth cones discussed above allows for a gradient of high <a href="/wiki/Posterior_(anatomy)" class="mw-redirect" title="Posterior (anatomy)">posterior</a> to low <a href="/wiki/Anterior" class="mw-redirect" title="Anterior">anterior</a> ephrin-A ligand expression in the SC to direct migrating RGCs axons from the temporal region of the retina that express a high level of EphA receptors toward targets in the anterior SC and RGCs from the nasal retina that have low EphA expression toward their final destination in the posterior SC.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">&#91;</span>16<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">&#91;</span>17<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">&#91;</span>18<span class="cite-bracket">&#93;</span></a></sup> Similarly, a gradient of <a href="/wiki/EFNB1" class="mw-redirect" title="EFNB1">ephrin-B1</a> expression along the medial-ventral axis of the SC directs the migration of <a href="/wiki/Dorsal_(anatomy)" class="mw-redirect" title="Dorsal (anatomy)">dorsal</a> and <a href="/wiki/Ventral" class="mw-redirect" title="Ventral">ventral</a> EphB-expressing RGCs to the lateral and medial SC respectively.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">&#91;</span>19<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Angiogenesis">Angiogenesis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=5" title="Edit section: Angiogenesis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:PDB_2bba_EBI.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/5/53/PDB_2bba_EBI.png/220px-PDB_2bba_EBI.png" decoding="async" width="220" height="165" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/5/53/PDB_2bba_EBI.png/330px-PDB_2bba_EBI.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/5/53/PDB_2bba_EBI.png/440px-PDB_2bba_EBI.png 2x" data-file-width="800" data-file-height="600" /></a><figcaption>The EphB4 receptor protein, known to assist in developmental and tumor angiogenesis.</figcaption></figure> <p>Ephrins promote angiogenesis in physiological and pathological conditions (e.g. cancer angiogenesis, neovascularisation in <a href="/wiki/Cerebral_arteriovenous_malformation" title="Cerebral arteriovenous malformation">cerebral arteriovenous malformation</a>).<sup id="cite_ref-pmid_=_22588055_20-0" class="reference"><a href="#cite_note-pmid_=_22588055-20"><span class="cite-bracket">&#91;</span>20<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-pmid_=_24517927_21-0" class="reference"><a href="#cite_note-pmid_=_24517927-21"><span class="cite-bracket">&#91;</span>21<span class="cite-bracket">&#93;</span></a></sup> In particular, <a href="/wiki/Ephrin-B2" class="mw-redirect" title="Ephrin-B2">Ephrin-B2</a> and <a href="/wiki/EphB4" class="mw-redirect" title="EphB4">EphB4</a> determine the arterial and venous fate of endothelial cells, respectively, though regulation of angiogenesis by mitigating expression in the <a href="/wiki/VEGF" class="mw-redirect" title="VEGF">VEGF</a> signalling pathway.<sup id="cite_ref-pmid_=_22588055_20-1" class="reference"><a href="#cite_note-pmid_=_22588055-20"><span class="cite-bracket">&#91;</span>20<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-Wang_2010_22-0" class="reference"><a href="#cite_note-Wang_2010-22"><span class="cite-bracket">&#91;</span>22<span class="cite-bracket">&#93;</span></a></sup> Ephrin-B2 affects VEGF-receptors (e.g.<a href="/wiki/VEGFR3" class="mw-redirect" title="VEGFR3">VEGFR3</a>) through forward and reverse signalling pathways.<sup id="cite_ref-Wang_2010_22-1" class="reference"><a href="#cite_note-Wang_2010-22"><span class="cite-bracket">&#91;</span>22<span class="cite-bracket">&#93;</span></a></sup> The Ephrin-B2 path extends to <a href="/wiki/Lymphangiogenesis" title="Lymphangiogenesis">lymphangiogenesis</a>, leading to internalization of VEGFR3 in cultured lymphatic endothelial cells.<sup id="cite_ref-Wang_2010_22-2" class="reference"><a href="#cite_note-Wang_2010-22"><span class="cite-bracket">&#91;</span>22<span class="cite-bracket">&#93;</span></a></sup> Though the role of ephrins in developmental angiogenesis is elucidated, tumor angiogenesis remains nebulous. Based on observations in <a href="/wiki/Ephrin-A2" class="mw-redirect" title="Ephrin-A2">Ephrin-A2</a> deficient mice, Ephrin-A2 may function in forward signalling in tumor angiogenesis; however, this ephrin does not contribute to vascular deformities during development.<sup id="cite_ref-Pasquale_2010_23-0" class="reference"><a href="#cite_note-Pasquale_2010-23"><span class="cite-bracket">&#91;</span>23<span class="cite-bracket">&#93;</span></a></sup> Moreover, Ephrin-B2 and EphB4 may also contribute to tumor angiogenesis in addition to their positions in development, though the exact mechanism remains unclear.<sup id="cite_ref-Pasquale_2010_23-1" class="reference"><a href="#cite_note-Pasquale_2010-23"><span class="cite-bracket">&#91;</span>23<span class="cite-bracket">&#93;</span></a></sup> The Ephrin B2/EphB4 and Ephrin B3/EphB1 receptor pairs contribute more to vasculogenesis in addition to angiogenesis whilst Ephrin A1/EphA2 appear to exclusively contribute to angiogenesis.<sup id="cite_ref-MoschReissenweber2010_24-0" class="reference"><a href="#cite_note-MoschReissenweber2010-24"><span class="cite-bracket">&#91;</span>24<span class="cite-bracket">&#93;</span></a></sup> </p><p>Several types of Ephrins and Eph receptors have been found to be upregulated in human cancers including breast, colon and liver cancers.<sup id="cite_ref-MoschReissenweber2010_24-1" class="reference"><a href="#cite_note-MoschReissenweber2010-24"><span class="cite-bracket">&#91;</span>24<span class="cite-bracket">&#93;</span></a></sup> Surprisingly, the downregulation of other types of Ephrins and their receptors may also contribute to tumorigenesis; namely, EphA1 in colorectal cancers and EphB6 in <a href="/wiki/Melanoma" title="Melanoma">melanoma</a>.<sup id="cite_ref-MoschReissenweber2010_24-2" class="reference"><a href="#cite_note-MoschReissenweber2010-24"><span class="cite-bracket">&#91;</span>24<span class="cite-bracket">&#93;</span></a></sup> Displaying similar utility, different ephrins incorporate similar mechanistic pathways to supplement growth of different structures. </p> <div class="mw-heading mw-heading3"><h3 id="Migration_factor_in_intestinal_epithelial_cell_migration">Migration factor in intestinal epithelial cell migration</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=6" title="Edit section: Migration factor in intestinal epithelial cell migration"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The ephrin protein family of class A and class B guides ligands with the EphB family cell-surface receptors to provide a steady, ordered, and specific migration of the <a href="/wiki/Intestinal_epithelial_cells" class="mw-redirect" title="Intestinal epithelial cells">intestinal epithelial cells</a> from the <a href="/wiki/Intestinal_gland" title="Intestinal gland">crypt</a><sup class="noprint Inline-Template" style="margin-left:0.1em; white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Please_clarify" title="Wikipedia:Please clarify"><span title="The text near this tag may need clarification or removal of jargon. (February 2016)">clarification needed</span></a></i>&#93;</sup> to <a href="/wiki/Intestinal_villus" title="Intestinal villus">villus</a>. The Wnt protein triggers expression of the EphB receptors deep within the crypt, leading to decreased Eph expression and increased ephrin ligand expression, the more superficial a progenitor cell's placement.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">&#91;</span>25<span class="cite-bracket">&#93;</span></a></sup> Migration is caused by a bi-directional signaling mechanism in which the engagement of the ephrin ligand with the EphB receptor regulates the actin cytoskeleton dynamics to cause a "repulsion". Cells remain in place once the interaction ceases to a stop. While the mucus secreting <a href="/wiki/Goblet_cells" class="mw-redirect" title="Goblet cells">Goblet cells</a> and the absorptive cells move towards the <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">lumen</a>, mature <a href="/wiki/Paneth_cells" class="mw-redirect" title="Paneth cells">Paneth cells</a> move in the opposite direction, to the bottom of the crypt, where they reside.<sup id="cite_ref-batlle_26-0" class="reference"><a href="#cite_note-batlle-26"><span class="cite-bracket">&#91;</span>26<span class="cite-bracket">&#93;</span></a></sup> With the exception of the ephrin ligand binding to EphA5, all other proteins from class A and B have been found in the intestine. However, ephrin proteins A4, A8, B2, and B4 have highest levels in fetal stage, and decline with age. </p><p>Experiments performed with Eph receptor knockout mice revealed disorder in the distribution of different cell types.<sup id="cite_ref-batlle_26-1" class="reference"><a href="#cite_note-batlle-26"><span class="cite-bracket">&#91;</span>26<span class="cite-bracket">&#93;</span></a></sup> Absorptive cells of various differentiation were mixed with the stem cells within the villi. Without the receptor, the Ephrin ligand was proved to be insufficient for the correct cell placement.<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">&#91;</span>27<span class="cite-bracket">&#93;</span></a></sup> Recent studies with knockout mice have also shown evidence of the ephrin-eph interaction indirect role in the suppression of <a href="/wiki/Colorectal_cancer" title="Colorectal cancer">colorectal cancer</a>. The development of adenomatous polyps created by uncontrolled outgrowth of epithelial cells is controlled by ephrin-eph interaction. Mice with <a href="/wiki/Adenomatous_polyposis_coli" title="Adenomatous polyposis coli">APC</a> mutation, without ephrin-B protein lack the means to prevent the spread of ephB positive tumor cells throughout the crypt-villi junction.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">&#91;</span>28<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Reverse_signaling">Reverse signaling</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=7" title="Edit section: Reverse signaling"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>One unique property of the ephrin ligands is that many have the capacity to initiate a "reverse" signal that is separate and distinct from the intracellular signal activated in Eph receptor-expressing cells. Although the mechanisms by which "reverse" signaling occurs are not completely understood, both ephrin-As and ephrin-Bs have been shown to mediate cellular responses that are distinct from those associated with activation of their corresponding receptors. Specifically, <a href="/wiki/EFNA5" class="mw-redirect" title="EFNA5">ephrin-A5</a> was shown to stimulate <a href="/wiki/Growth_cone" title="Growth cone">growth cone</a> spreading in spinal <a href="/wiki/Motor_neuron" title="Motor neuron">motor neurons</a><sup id="cite_ref-Marquadt_12-3" class="reference"><a href="#cite_note-Marquadt-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup> and <a href="/wiki/EFNB1" class="mw-redirect" title="EFNB1">ephrin-B1</a> was shown to promote <a href="/wiki/Dendrite" title="Dendrite">dendritic</a> spine maturation.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">&#91;</span>29<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ephrin&amp;action=edit&amp;section=8" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 33em;"> <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFEgeaKlein2007" class="citation journal cs1">Egea J, Klein R (May 2007). 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navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Intercellular_signaling_peptides_and_proteins" title="Template:Intercellular signaling peptides and proteins"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Intercellular_signaling_peptides_and_proteins" class="mw-redirect" title="Template talk:Intercellular signaling peptides and proteins"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Intercellular_signaling_peptides_and_proteins" title="Special:EditPage/Template:Intercellular signaling peptides and proteins"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Intercellular_signaling_peptides_and_proteins_/_ligands" style="font-size:114%;margin:0 4em">Intercellular signaling peptides and proteins / <a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">ligands</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite"><a href="/wiki/Growth_factor" title="Growth factor">Growth factors</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Epidermal_growth_factor" title="Epidermal growth factor">Epidermal growth factor</a></li> <li><a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">Fibroblast growth factor</a></li> <li><a href="/wiki/Nerve_growth_factor" title="Nerve growth factor">Nerve growth factor</a></li> <li><a href="/wiki/Platelet-derived_growth_factor" title="Platelet-derived growth factor">Platelet-derived growth factor</a></li> <li><a href="/wiki/Transforming_growth_factor_beta_superfamily" title="Transforming growth factor beta superfamily">Transforming growth factor beta superfamily</a></li> <li><a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">Vascular endothelial growth factor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite"><a class="mw-selflink selflink">Ephrin</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/EFNA1" class="mw-redirect" title="EFNA1">EFNA1</a></li> <li><a href="/wiki/EFNA2" class="mw-redirect" title="EFNA2">EFNA2</a></li> <li><a href="/wiki/EFNA3" class="mw-redirect" title="EFNA3">EFNA3</a></li> <li><a href="/wiki/EFNA4" class="mw-redirect" title="EFNA4">EFNA4</a></li> <li><a href="/wiki/EFNA5" class="mw-redirect" title="EFNA5">EFNA5</a></li> <li><a href="/wiki/EFNB1" class="mw-redirect" title="EFNB1">EFNB1</a></li> <li><a href="/wiki/EFNB2" class="mw-redirect" title="EFNB2">EFNB2</a></li> <li><a href="/wiki/EFNB3" class="mw-redirect" title="EFNB3">EFNB3</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background-color: AntiqueWhite">Other</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adipokine" title="Adipokine">Adipokine</a></li> <li><a href="/wiki/Agouti_signaling_protein" class="mw-redirect" title="Agouti signaling protein">Agouti signaling protein</a></li> <li><a href="/wiki/Agouti-related_protein" class="mw-redirect" title="Agouti-related protein">Agouti-related protein</a></li> <li><a href="/wiki/Angiogenic_protein" class="mw-redirect" title="Angiogenic protein">Angiogenic protein</a></li> <li><a href="/wiki/CCN_intercellular_signaling_protein" class="mw-redirect" title="CCN intercellular signaling protein">CCN intercellular signaling protein</a> <ul><li><a href="/wiki/Cysteine-rich_protein_61" class="mw-redirect" title="Cysteine-rich protein 61">Cysteine-rich protein 61</a></li> <li><a href="/wiki/Connective_tissue_growth_factor" class="mw-redirect" title="Connective tissue growth factor">Connective tissue growth factor</a></li> <li><a href="/wiki/Nephroblastoma_overexpressed_protein" class="mw-redirect" title="Nephroblastoma overexpressed protein">Nephroblastoma overexpressed protein</a></li></ul></li> <li><a href="/wiki/Cytokine" title="Cytokine">Cytokine</a></li> <li><a href="/wiki/Endothelin" title="Endothelin">Endothelin</a> <ul><li><a href="/wiki/EDN1" class="mw-redirect" title="EDN1">EDN1</a></li> <li><a href="/wiki/EDN2" class="mw-redirect" title="EDN2">EDN2</a></li> <li><a href="/wiki/EDN3" class="mw-redirect" title="EDN3">EDN3</a></li></ul></li> <li><a href="/wiki/Hedgehog_protein" class="mw-redirect" title="Hedgehog protein">Hedgehog protein</a></li> <li><a href="/wiki/Interferon" title="Interferon">Interferon</a></li> <li><a href="/wiki/Kinin" title="Kinin">Kinin</a></li> <li><a href="/wiki/Parathyroid_hormone-related_protein" title="Parathyroid hormone-related protein">Parathyroid hormone-related protein</a></li> <li><a href="/wiki/Semaphorin" title="Semaphorin">Semaphorin</a></li> <li><a href="/wiki/Somatomedin" title="Somatomedin">Somatomedin</a></li> <li><a href="/wiki/Tolloid-like_metalloproteinase" class="mw-redirect" title="Tolloid-like metalloproteinase">Tolloid-like metalloproteinase</a></li> <li><a href="/wiki/Tumor_necrosis_factor_alpha" class="mw-redirect" title="Tumor necrosis factor alpha">Tumor necrosis factor</a></li> <li><a href="/wiki/Wnt_protein" class="mw-redirect" title="Wnt protein">Wnt protein</a></li></ul> </div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="background-color: AntiqueWhite"><div><i>see also <a href="/wiki/Template:Extracellular_ligand_disorders" title="Template:Extracellular ligand disorders">extracellular ligand disorders</a></i></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Growth_factor_receptor_modulators" style="padding:3px"><table class="nowraplinks hlist mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Growth_factor_receptor_modulators" title="Template:Growth factor receptor modulators"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Growth_factor_receptor_modulators" title="Template talk:Growth factor receptor modulators"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Growth_factor_receptor_modulators" title="Special:EditPage/Template:Growth factor receptor modulators"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Growth_factor_receptor_modulators" style="font-size:114%;margin:0 4em"><a href="/wiki/Growth_factor_receptor" title="Growth factor receptor">Growth factor receptor</a> <a href="/wiki/Receptor_modulator" title="Receptor modulator">modulators</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Angiopoietin_receptor" title="Angiopoietin receptor">Angiopoietin</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Angiopoietin_1" title="Angiopoietin 1">Angiopoietin 1</a></li> <li><a href="/wiki/Angiopoietin_4" class="mw-redirect" title="Angiopoietin 4">Angiopoietin 4</a></li></ul> <ul><li><i>Antagonists:</i> <a href="/wiki/Angiopoietin_2" class="mw-redirect" title="Angiopoietin 2">Angiopoietin 2</a></li> <li><a href="/w/index.php?title=Angiopoietin_3&amp;action=edit&amp;redlink=1" class="new" title="Angiopoietin 3 (page does not exist)">Angiopoietin 3</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/w/index.php?title=CE-245677&amp;action=edit&amp;redlink=1" class="new" title="CE-245677 (page does not exist)">CE-245677</a></li> <li><a href="/wiki/Rebastinib" class="mw-redirect" title="Rebastinib">Rebastinib</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Evinacumab" title="Evinacumab">Evinacumab</a> (against angiopoietin 3)</li> <li><a href="/wiki/Nesvacumab" title="Nesvacumab">Nesvacumab</a> (against angiopoietin 2)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Ciliary_neurotrophic_factor_receptor" title="Ciliary neurotrophic factor receptor">CNTF</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Axokine" class="mw-redirect" title="Axokine">Axokine</a></li> <li><a href="/wiki/Ciliary_neurotrophic_factor_receptor" title="Ciliary neurotrophic factor receptor">CNTF</a></li> <li><a href="/w/index.php?title=Dapiclermin&amp;action=edit&amp;redlink=1" class="new" title="Dapiclermin (page does not exist)">Dapiclermin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">EGF (ErbB)</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">EGF<br /><small>(ErbB1/HER1)</small></a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists</i>: <a href="/wiki/Amphiregulin" title="Amphiregulin">Amphiregulin</a></li> <li><a href="/wiki/Betacellulin" title="Betacellulin">Betacellulin</a></li> <li><a href="/wiki/Epidermal_growth_factor" title="Epidermal growth factor">EGF (urogastrone)</a></li> <li><a href="/wiki/Epigen" title="Epigen">Epigen</a></li> <li><a href="/wiki/Epiregulin" title="Epiregulin">Epiregulin</a></li> <li><a href="/wiki/Heparin-binding_EGF-like_growth_factor" title="Heparin-binding EGF-like growth factor">Heparin-binding EGF-like growth factor (HB-EGF)</a></li> <li><a href="/wiki/Murodermin" title="Murodermin">Murodermin</a></li> <li><a href="/wiki/Nepidermin" title="Nepidermin">Nepidermin</a></li> <li><a href="/wiki/Transforming_growth_factor_alpha" class="mw-redirect" title="Transforming growth factor alpha">Transforming growth factor alpha (TGFα)</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Afatinib" title="Afatinib">Afatinib</a></li> <li><a href="/w/index.php?title=Agerafenib&amp;action=edit&amp;redlink=1" class="new" title="Agerafenib (page does not exist)">Agerafenib</a></li> <li><a href="/wiki/Brigatinib" title="Brigatinib">Brigatinib</a></li> <li><a href="/wiki/Canertinib" title="Canertinib">Canertinib</a></li> <li><a href="/wiki/Dacomitinib" title="Dacomitinib">Dacomitinib</a></li> <li><a href="/wiki/Erlotinib" title="Erlotinib">Erlotinib</a></li> <li><a href="/wiki/Gefitinib" title="Gefitinib">Gefitinib</a></li> <li><a href="/wiki/Grandinin" title="Grandinin">Grandinin</a></li> <li><a href="/wiki/Icotinib" title="Icotinib">Icotinib</a></li> <li><a href="/wiki/Lapatinib" title="Lapatinib">Lapatinib</a></li> <li><a href="/wiki/Neratinib" title="Neratinib">Neratinib</a></li> <li><a href="/wiki/Osimertinib" title="Osimertinib">Osimertinib</a></li> <li><a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li> <li><a href="/w/index.php?title=WHI-P_154&amp;action=edit&amp;redlink=1" class="new" title="WHI-P 154 (page does not exist)">WHI-P 154</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Cetuximab" title="Cetuximab">Cetuximab</a></li> <li><a href="/w/index.php?title=Depatuxizumab&amp;action=edit&amp;redlink=1" class="new" title="Depatuxizumab (page does not exist)">Depatuxizumab</a></li> <li><a href="/wiki/Depatuxizumab_mafodotin" title="Depatuxizumab mafodotin">Depatuxizumab mafodotin</a></li> <li><a href="/wiki/Futuximab" title="Futuximab">Futuximab</a></li> <li><a href="/wiki/Imgatuzumab" title="Imgatuzumab">Imgatuzumab</a></li> <li><a href="/wiki/Matuzumab" title="Matuzumab">Matuzumab</a></li> <li><a href="/wiki/Necitumumab" title="Necitumumab">Necitumumab</a></li> <li><a href="/wiki/Nimotuzumab" title="Nimotuzumab">Nimotuzumab</a></li> <li><a href="/wiki/Panitumumab" title="Panitumumab">Panitumumab</a></li> <li><a href="/wiki/Zalutumumab" title="Zalutumumab">Zalutumumab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/HER2/neu" class="mw-redirect" title="HER2/neu">ErbB2/HER2</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists</i>: <i>Unknown/none</i></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Ertumaxomab" title="Ertumaxomab">Ertumaxomab</a></li> <li><a href="/wiki/Pertuzumab" title="Pertuzumab">Pertuzumab</a></li> <li><a href="/wiki/Trastuzumab" title="Trastuzumab">Trastuzumab</a></li> <li><a href="/wiki/Trastuzumab_deruxtecan" title="Trastuzumab deruxtecan">Trastuzumab deruxtecan</a></li> <li><a href="/w/index.php?title=Trastuzumab_duocarmazine&amp;action=edit&amp;redlink=1" class="new" title="Trastuzumab duocarmazine (page does not exist)">Trastuzumab duocarmazine</a></li> <li><a href="/wiki/Trastuzumab_emtansine" title="Trastuzumab emtansine">Trastuzumab emtansine</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Afatinib" title="Afatinib">Afatinib</a></li> <li><a href="/wiki/Lapatinib" title="Lapatinib">Lapatinib</a></li> <li><a href="/wiki/Mubritinib" title="Mubritinib">Mubritinib</a></li> <li><a href="/wiki/Neratinib" title="Neratinib">Neratinib</a></li> <li><a href="/wiki/Tucatinib" title="Tucatinib">Tucatinib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/HER3" class="mw-redirect" title="HER3">ErbB3/HER3</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Neuregulin" title="Neuregulin">Neuregulins (heregulins)</a> (<a href="/wiki/Neuregulin-1" class="mw-redirect" title="Neuregulin-1">1</a>, <a href="/wiki/NRG2" class="mw-redirect" title="NRG2">2</a>, <a href="/wiki/CSPG5" title="CSPG5">6 (neuroglycan C)</a>)</li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Duligotumab" class="mw-redirect" title="Duligotumab">Duligotumab</a></li> <li><a href="/wiki/Patritumab" title="Patritumab">Patritumab</a></li> <li><a href="/wiki/Seribantumab" title="Seribantumab">Seribantumab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/HER4" class="mw-redirect" title="HER4">ErbB4/HER4</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Betacellulin" title="Betacellulin">Betacellulin</a></li> <li><a href="/wiki/Epigen" title="Epigen">Epigen</a></li> <li><a href="/wiki/Heparin-binding_EGF-like_growth_factor" title="Heparin-binding EGF-like growth factor">Heparin-binding EGF-like growth factor (HB-EGF)</a></li> <li><a href="/wiki/Neuregulin" title="Neuregulin">Neuregulins (heregulins)</a> (<a href="/wiki/Neuregulin-1" class="mw-redirect" title="Neuregulin-1">1</a>, <a href="/wiki/NRG2" class="mw-redirect" title="NRG2">2</a>, <a href="/wiki/NRG3" class="mw-redirect" title="NRG3">3</a>, <a href="/wiki/NRG4" class="mw-redirect" title="NRG4">4</a>, <a href="/w/index.php?title=Tomoregulin&amp;action=edit&amp;redlink=1" class="new" title="Tomoregulin (page does not exist)">5 (tomoregulin, TMEFF)</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Fibroblast_growth_factor_receptor" title="Fibroblast growth factor receptor">FGF</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Fibroblast_growth_factor_receptor_1" title="Fibroblast growth factor receptor 1">FGFR1</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/w/index.php?title=Ersofermin&amp;action=edit&amp;redlink=1" class="new" title="Ersofermin (page does not exist)">Ersofermin</a></li> <li><a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a> (<a href="/wiki/FGF1" class="mw-redirect" title="FGF1">1</a>, <a href="/wiki/FGF2" class="mw-redirect" title="FGF2">2 (bFGF)</a>, <a href="/wiki/FGF3" title="FGF3">3</a>, <a href="/wiki/FGF4" title="FGF4">4</a>, <a href="/wiki/FGF5" title="FGF5">5</a>, <a href="/wiki/FGF6" title="FGF6">6</a>, <a href="/wiki/FGF8" class="mw-redirect" title="FGF8">8</a>, <a href="/wiki/FGF10" title="FGF10">10 (KGF2)</a>, <a href="/wiki/FGF20" title="FGF20">20</a>)</li> <li><a href="/w/index.php?title=Repifermin&amp;action=edit&amp;redlink=1" class="new" title="Repifermin (page does not exist)">Repifermin</a></li> <li><a href="/wiki/Selpercatinib" title="Selpercatinib">Selpercatinib</a></li> <li><a href="/wiki/Trafermin" title="Trafermin">Trafermin</a></li> <li><a href="/w/index.php?title=Velafermin&amp;action=edit&amp;redlink=1" class="new" title="Velafermin (page does not exist)">Velafermin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Fibroblast_growth_factor_receptor_2" title="Fibroblast growth factor receptor 2">FGFR2</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/w/index.php?title=Ersofermin&amp;action=edit&amp;redlink=1" class="new" title="Ersofermin (page does not exist)">Ersofermin</a></li> <li><a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a> (<a href="/wiki/FGF1" class="mw-redirect" title="FGF1">1</a>, <a href="/wiki/FGF2" class="mw-redirect" title="FGF2">2 (bFGF)</a>, <a href="/wiki/FGF3" title="FGF3">3</a>, <a href="/wiki/FGF4" title="FGF4">4</a>, <a href="/wiki/FGF5" title="FGF5">5</a>, <a href="/wiki/FGF6" title="FGF6">6</a>, <a href="/wiki/FGF7" title="FGF7">7</a> (<a href="/wiki/Keratinocyte_growth_factor" title="Keratinocyte growth factor">KGF</a>), <a href="/wiki/FGF8" class="mw-redirect" title="FGF8">8</a>, <a href="/wiki/FGF9" title="FGF9">9</a>, <a href="/wiki/FGF10" title="FGF10">10 (KGF2)</a>, <a href="/wiki/FGF17" title="FGF17">17</a>, <a href="/wiki/FGF18" title="FGF18">18</a>, <a href="/wiki/FGF22" title="FGF22">22</a>)</li> <li><a href="/wiki/Palifermin" title="Palifermin">Palifermin</a></li> <li><a href="/w/index.php?title=Repifermin&amp;action=edit&amp;redlink=1" class="new" title="Repifermin (page does not exist)">Repifermin</a></li> <li><a href="/wiki/Selpercatinib" title="Selpercatinib">Selpercatinib</a></li> <li><a href="/wiki/Sprifermin" title="Sprifermin">Sprifermin</a></li> <li><a href="/wiki/Trafermin" title="Trafermin">Trafermin</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/w/index.php?title=Aprutumab&amp;action=edit&amp;redlink=1" class="new" title="Aprutumab (page does not exist)">Aprutumab</a></li> <li><a href="/w/index.php?title=Aprutumab_ixadotin&amp;action=edit&amp;redlink=1" class="new" title="Aprutumab ixadotin (page does not exist)">Aprutumab ixadotin</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Infigratinib" title="Infigratinib">Infigratinib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Fibroblast_growth_factor_receptor_3" title="Fibroblast growth factor receptor 3">FGFR3</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/w/index.php?title=Ersofermin&amp;action=edit&amp;redlink=1" class="new" title="Ersofermin (page does not exist)">Ersofermin</a></li> <li><a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a> (<a href="/wiki/FGF1" class="mw-redirect" title="FGF1">1</a>, <a href="/wiki/FGF2" class="mw-redirect" title="FGF2">2 (bFGF)</a>, <a href="/wiki/FGF4" title="FGF4">4</a>, <a href="/wiki/FGF8" class="mw-redirect" title="FGF8">8</a>, <a href="/wiki/FGF9" title="FGF9">9</a>, <a href="/wiki/FGF18" title="FGF18">18</a>, <a href="/wiki/FGF23" class="mw-redirect" title="FGF23">23</a>)</li> <li><a href="/wiki/Selpercatinib" title="Selpercatinib">Selpercatinib</a></li> <li><a href="/wiki/Sprifermin" title="Sprifermin">Sprifermin</a></li> <li><a href="/wiki/Trafermin" title="Trafermin">Trafermin</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Burosumab" title="Burosumab">Burosumab</a> (against FGF23)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Fibroblast_growth_factor_receptor_4" title="Fibroblast growth factor receptor 4">FGFR4</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/w/index.php?title=Ersofermin&amp;action=edit&amp;redlink=1" class="new" title="Ersofermin (page does not exist)">Ersofermin</a></li> <li><a href="/wiki/Fibroblast_growth_factor" title="Fibroblast growth factor">FGF</a> (<a href="/wiki/FGF1" class="mw-redirect" title="FGF1">1</a>, <a href="/wiki/FGF2" class="mw-redirect" title="FGF2">2 (bFGF)</a>, <a href="/wiki/FGF4" title="FGF4">4</a>, <a href="/wiki/FGF6" title="FGF6">6</a>, <a href="/wiki/FGF8" class="mw-redirect" title="FGF8">8</a>, <a href="/wiki/FGF9" title="FGF9">9</a>, <a href="/wiki/FGF19" title="FGF19">19</a>)</li> <li><a href="/wiki/Trafermin" title="Trafermin">Trafermin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Unsorted</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/FGF15/19" title="FGF15/19">FGF15/19</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Hepatocyte_growth_factor_receptor" title="Hepatocyte growth factor receptor">HGF (c-Met)</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists</i>: <a href="/wiki/Fosgonimeton" title="Fosgonimeton">Fosgonimeton</a></li> <li><a href="/wiki/Hepatocyte_growth_factor" title="Hepatocyte growth factor">Hepatocyte growth factor</a></li></ul> <ul><li><i>Potentiators:</i> <a href="/wiki/Dihexa" title="Dihexa">Dihexa (PNB-0408)</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/w/index.php?title=AM7_(drug)&amp;action=edit&amp;redlink=1" class="new" title="AM7 (drug) (page does not exist)">AM7</a></li> <li><a href="/w/index.php?title=AMG-458&amp;action=edit&amp;redlink=1" class="new" title="AMG-458 (page does not exist)">AMG-458</a></li> <li><a href="/w/index.php?title=Amuvatinib&amp;action=edit&amp;redlink=1" class="new" title="Amuvatinib (page does not exist)">Amuvatinib</a></li> <li><a href="/w/index.php?title=BMS-777607&amp;action=edit&amp;redlink=1" class="new" title="BMS-777607 (page does not exist)">BMS-777607</a></li> <li><a href="/wiki/Cabozantinib" title="Cabozantinib">Cabozantinib</a></li> <li><a href="/wiki/Capmatinib" title="Capmatinib">Capmatinib</a></li> <li><a href="/wiki/Crizotinib" title="Crizotinib">Crizotinib</a></li> <li><a href="/wiki/Foretinib" title="Foretinib">Foretinib</a></li> <li><a href="/w/index.php?title=Golvatinib&amp;action=edit&amp;redlink=1" class="new" title="Golvatinib (page does not exist)">Golvatinib</a></li> <li><a href="/w/index.php?title=INCB28060&amp;action=edit&amp;redlink=1" class="new" title="INCB28060 (page does not exist)">INCB28060</a></li> <li><a href="/w/index.php?title=JNJ-38877605&amp;action=edit&amp;redlink=1" class="new" title="JNJ-38877605 (page does not exist)">JNJ-38877605</a></li> <li><a href="/wiki/K252a" title="K252a">K252a</a></li> <li><a href="/w/index.php?title=MK-2461&amp;action=edit&amp;redlink=1" class="new" title="MK-2461 (page does not exist)">MK-2461</a></li> <li><a href="/w/index.php?title=PF-04217903&amp;action=edit&amp;redlink=1" class="new" title="PF-04217903 (page does not exist)">PF-04217903</a></li> <li><a href="/w/index.php?title=PF-2341066&amp;action=edit&amp;redlink=1" class="new" title="PF-2341066 (page does not exist)">PF-2341066</a></li> <li><a href="/w/index.php?title=PHA-665752&amp;action=edit&amp;redlink=1" class="new" title="PHA-665752 (page does not exist)">PHA-665752</a></li> <li><a href="/w/index.php?title=SU-11274&amp;action=edit&amp;redlink=1" class="new" title="SU-11274 (page does not exist)">SU-11274</a></li> <li><a href="/wiki/Tivantinib" title="Tivantinib">Tivantinib</a></li> <li><a href="/wiki/Volitinib" class="mw-redirect" title="Volitinib">Volitinib</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Emibetuzumab" title="Emibetuzumab">Emibetuzumab</a></li> <li><a href="/wiki/Ficlatuzumab" title="Ficlatuzumab">Ficlatuzumab</a></li> <li><a href="/wiki/Flanvotumab" title="Flanvotumab">Flanvotumab</a></li> <li><a href="/wiki/Onartuzumab" title="Onartuzumab">Onartuzumab</a></li> <li><a href="/wiki/Rilotumumab" title="Rilotumumab">Rilotumumab</a></li> <li><a href="/w/index.php?title=Telisotuzumab&amp;action=edit&amp;redlink=1" class="new" title="Telisotuzumab (page does not exist)">Telisotuzumab</a></li> <li><a href="/wiki/Telisotuzumab_vedotin" title="Telisotuzumab vedotin">Telisotuzumab vedotin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Somatomedin_receptor" title="Somatomedin receptor">IGF</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Insulin-like_growth_factor_1_receptor" title="Insulin-like growth factor 1 receptor">IGF-1</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists</i>: <a href="/wiki/Des(1-3)IGF-1" title="Des(1-3)IGF-1">des(1-3)IGF-1</a></li> <li><a href="/wiki/Insulin-like_growth_factor_1" title="Insulin-like growth factor 1">Insulin-like growth factor-1 (somatomedin C)</a></li> <li><a href="/wiki/IGF-1_LR3" title="IGF-1 LR3">IGF-1 LR3</a></li> <li><a href="/wiki/Insulin-like_growth_factor_2" title="Insulin-like growth factor 2">Insulin-like growth factor-2 (somatomedin A)</a></li> <li><a href="/wiki/Insulin" title="Insulin">Insulin</a></li> <li><a href="/wiki/Mecasermin" title="Mecasermin">Mecasermin</a></li> <li><a href="/wiki/Mecasermin_rinfabate" title="Mecasermin rinfabate">Mecasermin rinfabate</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=BMS-754807&amp;action=edit&amp;redlink=1" class="new" title="BMS-754807 (page does not exist)">BMS-754807</a></li> <li><a href="/wiki/Linsitinib" title="Linsitinib">Linsitinib</a></li> <li><a href="/w/index.php?title=NVP-ADW742&amp;action=edit&amp;redlink=1" class="new" title="NVP-ADW742 (page does not exist)">NVP-ADW742</a></li> <li><a href="/w/index.php?title=NVP-AEW541&amp;action=edit&amp;redlink=1" class="new" title="NVP-AEW541 (page does not exist)">NVP-AEW541</a></li> <li><a href="/w/index.php?title=OSl-906&amp;action=edit&amp;redlink=1" class="new" title="OSl-906 (page does not exist)">OSl-906</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/w/index.php?title=AVE-1642&amp;action=edit&amp;redlink=1" class="new" title="AVE-1642 (page does not exist)">AVE-1642</a></li> <li><a href="/wiki/Cixutumumab" title="Cixutumumab">Cixutumumab</a></li> <li><a href="/wiki/Dalotuzumab" title="Dalotuzumab">Dalotuzumab</a></li> <li><a href="/wiki/Figitumumab" title="Figitumumab">Figitumumab</a></li> <li><a href="/wiki/Ganitumab" title="Ganitumab">Ganitumab</a></li> <li><a href="/wiki/Robatumumab" title="Robatumumab">Robatumumab</a></li> <li><a href="/w/index.php?title=R1507&amp;action=edit&amp;redlink=1" class="new" title="R1507 (page does not exist)">R1507</a></li> <li><a href="/wiki/Teprotumumab" title="Teprotumumab">Teprotumumab</a></li> <li><a href="/w/index.php?title=Xentuzumab&amp;action=edit&amp;redlink=1" class="new" title="Xentuzumab (page does not exist)">Xentuzumab</a> (against IGF-1 and IGF-2)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Insulin-like_growth_factor_2_receptor" title="Insulin-like growth factor 2 receptor">IGF-2</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists</i>: <a href="/wiki/Insulin-like_growth_factor_2" title="Insulin-like growth factor 2">Insulin-like growth factor-2 (somatomedin A)</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Dusigitumab" title="Dusigitumab">Dusigitumab</a></li> <li><a href="/w/index.php?title=Xentuzumab&amp;action=edit&amp;redlink=1" class="new" title="Xentuzumab (page does not exist)">Xentuzumab</a> (against IGF-1 and IGF-2)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Others</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Binding proteins:</i> <a href="/wiki/Insulin-like_growth_factor-binding_protein" title="Insulin-like growth factor-binding protein">IGFBP</a> (<a href="/wiki/IGFBP1" title="IGFBP1">1</a>, <a href="/wiki/IGFBP2" title="IGFBP2">2</a>, <a href="/wiki/IGFBP3" title="IGFBP3">3</a>, <a href="/wiki/IGFBP4" title="IGFBP4">4</a>, <a href="/wiki/IGFBP5" title="IGFBP5">5</a>, <a href="/wiki/IGFBP6" title="IGFBP6">6</a>, <a href="/wiki/IGFBP7" title="IGFBP7">7</a>)</li></ul> <ul><li><i>Cleavage products/derivatives with unknown target:</i> <a href="/w/index.php?title=Glypromate&amp;action=edit&amp;redlink=1" class="new" title="Glypromate (page does not exist)">Glypromate (GPE, (1-3)IGF-1)</a></li> <li><a href="/wiki/Trofinetide" title="Trofinetide">Trofinetide</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Low-affinity_nerve_growth_factor_receptor" title="Low-affinity nerve growth factor receptor">LNGF (p75<sup>NTR</sup>)</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Brain-derived_neurotrophic_factor" title="Brain-derived neurotrophic factor">BDNF</a></li> <li><a href="/wiki/BNN-20" title="BNN-20">BNN-20</a></li> <li><a href="/wiki/BNN-27" title="BNN-27">BNN-27</a></li> <li><a href="/wiki/Cenegermin" title="Cenegermin">Cenegermin</a></li> <li><a href="/wiki/Dehydroepiandrosterone" title="Dehydroepiandrosterone">DHEA</a></li> <li><a href="/wiki/Dehydroepiandrosterone_sulfate" title="Dehydroepiandrosterone sulfate">DHEA-S</a></li> <li><a href="/wiki/Nerve_growth_factor" title="Nerve growth factor">NGF</a></li> <li><a href="/wiki/Neurotrophin-3" title="Neurotrophin-3">NT-3</a></li> <li><a href="/wiki/Neurotrophin-4" title="Neurotrophin-4">NT-4</a></li></ul> <ul><li><i>Antagonists:</i> <a href="/w/index.php?title=ALE-0540&amp;action=edit&amp;redlink=1" class="new" title="ALE-0540 (page does not exist)">ALE-0540</a></li> <li><a href="/wiki/Dexamethasone" title="Dexamethasone">Dexamethasone</a></li> <li><a href="/w/index.php?title=EVT-901&amp;action=edit&amp;redlink=1" class="new" title="EVT-901 (page does not exist)">EVT-901 (SAR-127963)</a></li> <li><a href="/wiki/Testosterone" title="Testosterone">Testosterone</a></li></ul> <ul><li><i>Antibodies:</i> <i>Against NGF:</i> <a href="/w/index.php?title=ABT-110&amp;action=edit&amp;redlink=1" class="new" title="ABT-110 (page does not exist)">ABT-110 (PG110)</a></li> <li><a href="/w/index.php?title=ASP-6294&amp;action=edit&amp;redlink=1" class="new" title="ASP-6294 (page does not exist)">ASP-6294</a></li> <li><a href="/wiki/Fasinumab" title="Fasinumab">Fasinumab</a></li> <li><a href="/wiki/Frunevetmab" title="Frunevetmab">Frunevetmab</a></li> <li><a href="/wiki/Fulranumab" title="Fulranumab">Fulranumab</a></li> <li><a href="/w/index.php?title=MEDI-578&amp;action=edit&amp;redlink=1" class="new" title="MEDI-578 (page does not exist)">MEDI-578</a></li> <li><a href="/w/index.php?title=Ranevetmab&amp;action=edit&amp;redlink=1" class="new" title="Ranevetmab (page does not exist)">Ranevetmab</a></li> <li><a href="/wiki/Tanezumab" title="Tanezumab">Tanezumab</a></li></ul> <ul><li><i>Aptamers:</i> <i>Against NGF:</i> <a href="/w/index.php?title=RBM-004&amp;action=edit&amp;redlink=1" class="new" title="RBM-004 (page does not exist)">RBM-004</a></li></ul> <ul><li><i>Decoy receptors:</i> <a href="/w/index.php?title=LEVI-04&amp;action=edit&amp;redlink=1" class="new" title="LEVI-04 (page does not exist)">LEVI-04 (p75<sup>NTR</sup>-Fc)</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Platelet-derived_growth_factor_receptor" title="Platelet-derived growth factor receptor">PDGF</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Becaplermin" title="Becaplermin">Becaplermin</a></li> <li><a href="/wiki/Platelet-derived_growth_factor" title="Platelet-derived growth factor">Platelet-derived growth factor</a> (<a href="/wiki/PDGFA" title="PDGFA">A</a>, <a href="/wiki/PDGFB" title="PDGFB">B</a>, <a href="/wiki/PDGFC" title="PDGFC">C</a>, <a href="/wiki/PDGFD" title="PDGFD">D</a>)</li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Agerafenib&amp;action=edit&amp;redlink=1" class="new" title="Agerafenib (page does not exist)">Agerafenib</a></li> <li><a href="/wiki/Avapritinib" title="Avapritinib">Avapritinib</a></li> <li><a href="/wiki/Axitinib" title="Axitinib">Axitinib</a></li> <li><a href="/wiki/Crenolanib" title="Crenolanib">Crenolanib</a></li> <li><a href="/wiki/Imatinib" title="Imatinib">Imatinib</a></li> <li><a href="/wiki/Lenvatinib" title="Lenvatinib">Lenvatinib</a></li> <li><a href="/wiki/Masitinib" title="Masitinib">Masitinib</a></li> <li><a href="/wiki/Motesanib" title="Motesanib">Motesanib</a></li> <li><a href="/wiki/Nintedanib" title="Nintedanib">Nintedanib</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Radotinib" title="Radotinib">Radotinib</a></li> <li><a href="/wiki/Quizartinib" title="Quizartinib">Quizartinib</a></li> <li><a href="/wiki/Ripretinib" title="Ripretinib">Ripretinib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Toceranib" title="Toceranib">Toceranib</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Olaratumab" title="Olaratumab">Olaratumab</a></li> <li><a href="/wiki/Ramucirumab" title="Ramucirumab">Ramucirumab</a></li> <li><a href="/wiki/Tovetumab" title="Tovetumab">Tovetumab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/RET_proto-oncogene" title="RET proto-oncogene">RET (GFL)</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/GFR%CE%B11" class="mw-redirect" title="GFRα1">GFRα1</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Glial_cell_line-derived_neurotrophic_factor" title="Glial cell line-derived neurotrophic factor">Glial cell line-derived neurotrophic factor (GDNF)</a></li> <li><a href="/w/index.php?title=Liatermin&amp;action=edit&amp;redlink=1" class="new" title="Liatermin (page does not exist)">Liatermin</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/GFR%CE%B12" class="mw-redirect" title="GFRα2">GFRα2</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Neurturin" title="Neurturin">Neurturin (NRTN)</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/GFR%CE%B13" class="mw-redirect" title="GFRα3">GFRα3</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Artemin" title="Artemin">Artemin (ARTN)</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/GFR%CE%B14" class="mw-redirect" title="GFRα4">GFRα4</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Persephin" title="Persephin">Persephin (PSPN)</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Unsorted</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Agerafenib&amp;action=edit&amp;redlink=1" class="new" title="Agerafenib (page does not exist)">Agerafenib</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/CD117" class="mw-redirect" title="CD117">SCF (c-Kit)</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Ancestim" title="Ancestim">Ancestim</a></li> <li><a href="/wiki/Stem_cell_factor" title="Stem cell factor">Stem cell factor</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Agerafenib&amp;action=edit&amp;redlink=1" class="new" title="Agerafenib (page does not exist)">Agerafenib</a></li> <li><a href="/wiki/Axitinib" title="Axitinib">Axitinib</a></li> <li><a href="/wiki/Dasatinib" title="Dasatinib">Dasatinib</a></li> <li><a href="/wiki/Imatinib" title="Imatinib">Imatinib</a></li> <li><a href="/wiki/Masitinib" title="Masitinib">Masitinib</a></li> <li><a href="/wiki/Nilotinib" title="Nilotinib">Nilotinib</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Quizartinib" title="Quizartinib">Quizartinib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Toceranib" title="Toceranib">Toceranib</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Transforming_growth_factor_beta_receptor" class="mw-redirect" title="Transforming growth factor beta receptor">TGFβ</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>See <a href="/wiki/Template:TGF%CE%B2_receptor_superfamily_modulators" title="Template:TGFβ receptor superfamily modulators">here</a> instead.</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Trk_receptor" title="Trk receptor">Trk</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/TrkA_receptor" class="mw-redirect" title="TrkA receptor">TrkA</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Amitriptyline" title="Amitriptyline">Amitriptyline</a></li> <li><a href="/wiki/BNN-20" title="BNN-20">BNN-20</a></li> <li><a href="/wiki/BNN-27" title="BNN-27">BNN-27</a></li> <li><a href="/wiki/Cenegermin" title="Cenegermin">Cenegermin</a></li> <li><a href="/wiki/Dehydroepiandrosterone" title="Dehydroepiandrosterone">DHEA</a></li> <li><a href="/wiki/Dehydroepiandrosterone_sulfate" title="Dehydroepiandrosterone sulfate">DHEA-S</a></li> <li><a href="/w/index.php?title=Gambogic_amide&amp;action=edit&amp;redlink=1" class="new" title="Gambogic amide (page does not exist)">Gambogic amide</a></li> <li><a href="/wiki/Nerve_growth_factor" title="Nerve growth factor">NGF</a></li> <li><a href="/wiki/Tavilermide" title="Tavilermide">Tavilermide</a></li></ul> <ul><li><i>Antagonists:</i> <a href="/w/index.php?title=ALE-0540&amp;action=edit&amp;redlink=1" class="new" title="ALE-0540 (page does not exist)">ALE-0540</a></li> <li><a href="/wiki/Dexamethasone" title="Dexamethasone">Dexamethasone</a></li> <li><a href="/wiki/FX007" class="mw-redirect" title="FX007">FX007</a></li> <li><a href="/wiki/Testosterone" title="Testosterone">Testosterone</a></li></ul> <ul><li><i>Negative allosteric modulators:</i> <a href="/w/index.php?title=VM-902A&amp;action=edit&amp;redlink=1" class="new" title="VM-902A (page does not exist)">VM-902A</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/w/index.php?title=AZD-6918&amp;action=edit&amp;redlink=1" class="new" title="AZD-6918 (page does not exist)">AZD-6918</a></li> <li><a href="/w/index.php?title=CE-245677&amp;action=edit&amp;redlink=1" class="new" title="CE-245677 (page does not exist)">CE-245677</a></li> <li><a href="/w/index.php?title=CH-7057288&amp;action=edit&amp;redlink=1" class="new" title="CH-7057288 (page does not exist)">CH-7057288</a></li> <li><a href="/w/index.php?title=DS-6051&amp;action=edit&amp;redlink=1" class="new" title="DS-6051 (page does not exist)">DS-6051</a></li> <li><a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a></li> <li><a href="/w/index.php?title=GZ-389988&amp;action=edit&amp;redlink=1" class="new" title="GZ-389988 (page does not exist)">GZ-389988</a></li> <li><a href="/wiki/K252a" title="K252a">K252a</a></li> <li><a href="/wiki/Larotrectinib" title="Larotrectinib">Larotrectinib</a></li> <li><a href="/wiki/Lestaurtinib" title="Lestaurtinib">Lestaurtinib</a></li> <li><a href="/w/index.php?title=Milciclib&amp;action=edit&amp;redlink=1" class="new" title="Milciclib (page does not exist)">Milciclib</a></li> <li><a href="/w/index.php?title=ONO-4474&amp;action=edit&amp;redlink=1" class="new" title="ONO-4474 (page does not exist)">ONO-4474</a></li> <li><a href="/w/index.php?title=ONO-5390556&amp;action=edit&amp;redlink=1" class="new" title="ONO-5390556 (page does not exist)">ONO-5390556</a></li> <li><a href="/w/index.php?title=PLX-7486&amp;action=edit&amp;redlink=1" class="new" title="PLX-7486 (page does not exist)">PLX-7486</a></li> <li><a href="/wiki/Rebastinib" class="mw-redirect" title="Rebastinib">Rebastinib</a></li> <li><a href="/w/index.php?title=SNA-120&amp;action=edit&amp;redlink=1" class="new" title="SNA-120 (page does not exist)">SNA-120 (pegylated K252a)</a>)</li></ul> <ul><li><i>Antibodies:</i> <i>Against TrkA:</i> <a href="/w/index.php?title=GBR-900&amp;action=edit&amp;redlink=1" class="new" title="GBR-900 (page does not exist)">GBR-900</a>; <i>Against NGF:</i> <a href="/w/index.php?title=ABT-110&amp;action=edit&amp;redlink=1" class="new" title="ABT-110 (page does not exist)">ABT-110 (PG110)</a></li> <li><a href="/w/index.php?title=ASP-6294&amp;action=edit&amp;redlink=1" class="new" title="ASP-6294 (page does not exist)">ASP-6294</a></li> <li><a href="/wiki/Fasinumab" title="Fasinumab">Fasinumab</a></li> <li><a href="/wiki/Frunevetmab" title="Frunevetmab">Frunevetmab</a></li> <li><a href="/wiki/Fulranumab" title="Fulranumab">Fulranumab</a></li> <li><a href="/w/index.php?title=MEDI-578&amp;action=edit&amp;redlink=1" class="new" title="MEDI-578 (page does not exist)">MEDI-578</a></li> <li><a href="/w/index.php?title=Ranevetmab&amp;action=edit&amp;redlink=1" class="new" title="Ranevetmab (page does not exist)">Ranevetmab</a></li> <li><a href="/wiki/Tanezumab" title="Tanezumab">Tanezumab</a></li></ul> <ul><li><i>Aptamers:</i> <i>Against NGF:</i> <a href="/w/index.php?title=RBM-004&amp;action=edit&amp;redlink=1" class="new" title="RBM-004 (page does not exist)">RBM-004</a></li></ul> <ul><li><i>Decoy receptors:</i> <a href="/w/index.php?title=ReN-1820&amp;action=edit&amp;redlink=1" class="new" title="ReN-1820 (page does not exist)">ReN-1820 (TrkAd5)</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/TrkB_receptor" class="mw-redirect" title="TrkB receptor">TrkB</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/w/index.php?title=3,7-Dihydroxyflavone&amp;action=edit&amp;redlink=1" class="new" title="3,7-Dihydroxyflavone (page does not exist)">3,7-DHF</a></li> <li><a href="/w/index.php?title=3,7,8,2%27-Tetrahydroxyflavone&amp;action=edit&amp;redlink=1" class="new" title="3,7,8,2&#39;-Tetrahydroxyflavone (page does not exist)">3,7,8,2'-THF</a></li> <li><a href="/wiki/4%27-Dimethylamino-7,8-dihydroxyflavone" class="mw-redirect" title="4&#39;-Dimethylamino-7,8-dihydroxyflavone">4'-DMA-7,8-DHF</a></li> <li><a href="/w/index.php?title=7,3%E2%80%B2-Dihydroxyflavone&amp;action=edit&amp;redlink=1" class="new" title="7,3′-Dihydroxyflavone (page does not exist)">7,3'-DHF</a></li> <li><a href="/wiki/7,8-Dihydroxyflavone" class="mw-redirect" title="7,8-Dihydroxyflavone">7,8-DHF</a></li> <li><a href="/w/index.php?title=7,8,2%27-Trihydroxyflavone&amp;action=edit&amp;redlink=1" class="new" title="7,8,2&#39;-Trihydroxyflavone (page does not exist)">7,8,2'-THF</a></li> <li><a href="/wiki/7,8,3%27-Trihydroxyflavone" title="7,8,3&#39;-Trihydroxyflavone">7,8,3'-THF</a></li> <li><a href="/wiki/Amitriptyline" title="Amitriptyline">Amitriptyline</a></li> <li><a href="/wiki/Brain-derived_neurotrophic_factor" title="Brain-derived neurotrophic factor">BDNF</a></li> <li><a href="/wiki/BNN-20" title="BNN-20">BNN-20</a></li> <li><a href="/wiki/Deoxygedunin" title="Deoxygedunin">Deoxygedunin</a></li> <li><a href="/wiki/Deprenyl" title="Deprenyl">Deprenyl</a></li> <li><a href="/wiki/Diosmetin" title="Diosmetin">Diosmetin</a></li> <li><a href="/w/index.php?title=DMAQ-B1&amp;action=edit&amp;redlink=1" class="new" title="DMAQ-B1 (page does not exist)">DMAQ-B1</a></li> <li><a href="/wiki/HIOC" title="HIOC">HIOC</a></li> <li><a href="/wiki/LM22A-4" title="LM22A-4">LM22A-4</a></li> <li><a href="/wiki/N-Acetylserotonin" title="N-Acetylserotonin">N-Acetylserotonin</a></li> <li><a href="/wiki/Neurotrophin-3" title="Neurotrophin-3">NT-3</a></li> <li><a href="/wiki/Neurotrophin-4" title="Neurotrophin-4">NT-4</a></li> <li><a href="/wiki/Norwogonin" title="Norwogonin">Norwogonin (5,7,8-THF)</a></li> <li><a href="/wiki/R7_(drug)" title="R7 (drug)">R7</a></li> <li><a href="/wiki/R13_(drug)" title="R13 (drug)">R13</a></li> <li><a href="/w/index.php?title=TDP6&amp;action=edit&amp;redlink=1" class="new" title="TDP6 (page does not exist)">TDP6</a></li></ul> <ul><li><i>Antagonists:</i> <a href="/wiki/ANA-12" title="ANA-12">ANA-12</a></li> <li><a href="/wiki/Cyclotraxin_B" title="Cyclotraxin B">Cyclotraxin B</a></li> <li><a href="/wiki/Gossypetin" title="Gossypetin">Gossypetin (3,5,7,8,3',4'-HHF)</a></li></ul> <ul><li><i>Ligands:</i> <a href="/wiki/Dehydroepiandrosterone" title="Dehydroepiandrosterone">DHEA</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/w/index.php?title=AZD-6918&amp;action=edit&amp;redlink=1" class="new" title="AZD-6918 (page does not exist)">AZD-6918</a></li> <li><a href="/w/index.php?title=CE-245677&amp;action=edit&amp;redlink=1" class="new" title="CE-245677 (page does not exist)">CE-245677</a></li> <li><a href="/w/index.php?title=CH-7057288&amp;action=edit&amp;redlink=1" class="new" title="CH-7057288 (page does not exist)">CH-7057288</a></li> <li><a href="/w/index.php?title=DS-6051&amp;action=edit&amp;redlink=1" class="new" title="DS-6051 (page does not exist)">DS-6051</a></li> <li><a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a></li> <li><a href="/w/index.php?title=GZ-389988&amp;action=edit&amp;redlink=1" class="new" title="GZ-389988 (page does not exist)">GZ-389988</a></li> <li><a href="/wiki/K252a" title="K252a">K252a</a></li> <li><a href="/wiki/Larotrectinib" title="Larotrectinib">Larotrectinib</a></li> <li><a href="/wiki/Lestaurtinib" title="Lestaurtinib">Lestaurtinib</a></li> <li><a href="/w/index.php?title=ONO-4474&amp;action=edit&amp;redlink=1" class="new" title="ONO-4474 (page does not exist)">ONO-4474</a></li> <li><a href="/w/index.php?title=ONO-5390556&amp;action=edit&amp;redlink=1" class="new" title="ONO-5390556 (page does not exist)">ONO-5390556</a></li> <li><a href="/w/index.php?title=PLX-7486&amp;action=edit&amp;redlink=1" class="new" title="PLX-7486 (page does not exist)">PLX-7486</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/TrkC_receptor" class="mw-redirect" title="TrkC receptor">TrkC</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/BNN-20" title="BNN-20">BNN-20</a></li> <li><a href="/wiki/Dehydroepiandrosterone" title="Dehydroepiandrosterone">DHEA</a></li> <li><a href="/wiki/Neurotrophin-3" title="Neurotrophin-3">NT-3</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/w/index.php?title=AZD-6918&amp;action=edit&amp;redlink=1" class="new" title="AZD-6918 (page does not exist)">AZD-6918</a></li> <li><a href="/w/index.php?title=CE-245677&amp;action=edit&amp;redlink=1" class="new" title="CE-245677 (page does not exist)">CE-245677</a></li> <li><a href="/w/index.php?title=CH-7057288&amp;action=edit&amp;redlink=1" class="new" title="CH-7057288 (page does not exist)">CH-7057288</a></li> <li><a href="/w/index.php?title=DS-6051&amp;action=edit&amp;redlink=1" class="new" title="DS-6051 (page does not exist)">DS-6051</a></li> <li><a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a></li> <li><a href="/w/index.php?title=GZ-389988&amp;action=edit&amp;redlink=1" class="new" title="GZ-389988 (page does not exist)">GZ-389988</a></li> <li><a href="/wiki/K252a" title="K252a">K252a</a></li> <li><a href="/wiki/Larotrectinib" title="Larotrectinib">Larotrectinib</a></li> <li><a href="/wiki/Lestaurtinib" title="Lestaurtinib">Lestaurtinib</a></li> <li><a href="/w/index.php?title=ONO-4474&amp;action=edit&amp;redlink=1" class="new" title="ONO-4474 (page does not exist)">ONO-4474</a></li> <li><a href="/w/index.php?title=ONO-5390556&amp;action=edit&amp;redlink=1" class="new" title="ONO-5390556 (page does not exist)">ONO-5390556</a></li> <li><a href="/w/index.php?title=PLX-7486&amp;action=edit&amp;redlink=1" class="new" title="PLX-7486 (page does not exist)">PLX-7486</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Vascular_endothelial_growth_factor_receptor" class="mw-redirect" title="Vascular endothelial growth factor receptor">VEGF</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Agonists:</i> <a href="/wiki/Placental_growth_factor" title="Placental growth factor">Placental growth factor (PGF)</a></li> <li><a href="/wiki/Ripretinib" title="Ripretinib">Ripretinib</a></li> <li><a href="/w/index.php?title=Telbermin&amp;action=edit&amp;redlink=1" class="new" title="Telbermin (page does not exist)">Telbermin</a></li> <li><a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a> (<a href="/wiki/Vascular_endothelial_growth_factor_A" title="Vascular endothelial growth factor A">A</a>, <a href="/wiki/Vascular_endothelial_growth_factor_B" title="Vascular endothelial growth factor B">B</a>, <a href="/wiki/Vascular_endothelial_growth_factor_C" title="Vascular endothelial growth factor C">C</a>, <a href="/wiki/Vascular_endothelial_growth_factor_D" class="mw-redirect" title="Vascular endothelial growth factor D">D (FIGF)</a>)</li></ul> <ul><li><i>Allosteric modulators:</i> <a href="/wiki/Cyclotraxin_B" title="Cyclotraxin B">Cyclotraxin B</a></li></ul> <ul><li><i>Kinase inhibitors:</i> <a href="/w/index.php?title=Agerafenib&amp;action=edit&amp;redlink=1" class="new" title="Agerafenib (page does not exist)">Agerafenib</a></li> <li><a href="/w/index.php?title=Altiratinib&amp;action=edit&amp;redlink=1" class="new" title="Altiratinib (page does not exist)">Altiratinib</a></li> <li><a href="/wiki/Axitinib" title="Axitinib">Axitinib</a></li> <li><a href="/wiki/Cabozantinib" title="Cabozantinib">Cabozantinib</a></li> <li><a href="/wiki/Cediranib" title="Cediranib">Cediranib</a></li> <li><a href="/wiki/Fruquintinib" title="Fruquintinib">Fruquintinib</a></li> <li><a href="/wiki/Lapatinib" title="Lapatinib">Lapatinib</a></li> <li><a href="/wiki/Lenvatinib" title="Lenvatinib">Lenvatinib</a></li> <li><a href="/wiki/Motesanib" title="Motesanib">Motesanib</a></li> <li><a href="/wiki/Nintedanib" title="Nintedanib">Nintedanib</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Pegaptanib" title="Pegaptanib">Pegaptanib</a></li> <li><a href="/wiki/Rebastinib" class="mw-redirect" title="Rebastinib">Rebastinib</a></li> <li><a href="/wiki/Regorafenib" title="Regorafenib">Regorafenib</a></li> <li><a href="/wiki/Semaxanib" title="Semaxanib">Semaxanib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Toceranib" title="Toceranib">Toceranib</a></li> <li><a href="/wiki/Tivozanib" title="Tivozanib">Tivozanib</a></li> <li><a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li> <li><a href="/w/index.php?title=WHI-P_154&amp;action=edit&amp;redlink=1" class="new" title="WHI-P 154 (page does not exist)">WHI-P 154</a></li></ul> <ul><li><i>Antibodies:</i> <a href="/wiki/Alacizumab_pegol" title="Alacizumab pegol">Alacizumab pegol</a></li> <li><a href="/wiki/Bevacizumab" title="Bevacizumab">Bevacizumab</a></li> <li><a href="/wiki/Icrucumab" title="Icrucumab">Icrucumab</a></li> <li><a href="/wiki/Ramucirumab" title="Ramucirumab">Ramucirumab</a></li> <li><a href="/wiki/Ranibizumab" title="Ranibizumab">Ranibizumab</a></li></ul> <ul><li><i>Decoy receptors:</i> <a href="/wiki/Aflibercept" title="Aflibercept">Aflibercept</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Others</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Additional growth factors:</i> <a href="/wiki/Adrenomedullin" title="Adrenomedullin">Adrenomedullin</a></li> <li><a href="/wiki/Colony-stimulating_factor" title="Colony-stimulating factor">Colony-stimulating factors</a> (see <a href="/wiki/Template:Cytokine_receptor_modulators" title="Template:Cytokine receptor modulators">here</a> instead)</li> <li><a href="/wiki/Connective_tissue_growth_factor" class="mw-redirect" title="Connective tissue growth factor">Connective tissue growth factor (CTGF)</a></li> <li><a class="mw-selflink selflink">Ephrins</a> (<a href="/wiki/EFNA1" class="mw-redirect" title="EFNA1">A1</a>, <a href="/wiki/EFNA2" class="mw-redirect" title="EFNA2">A2</a>, <a href="/wiki/EFNA3" class="mw-redirect" title="EFNA3">A3</a>, <a href="/wiki/EFNA4" class="mw-redirect" title="EFNA4">A4</a>, <a href="/wiki/EFNA5" class="mw-redirect" title="EFNA5">A5</a>, <a href="/wiki/EFNB1" class="mw-redirect" title="EFNB1">B1</a>, <a href="/wiki/EFNB2" class="mw-redirect" title="EFNB2">B2</a>, <a href="/wiki/EFNB3" class="mw-redirect" title="EFNB3">B3</a>)</li> <li><a href="/wiki/Erythropoietin" title="Erythropoietin">Erythropoietin</a> (see <a href="/wiki/Template:Cytokine_receptor_modulators" title="Template:Cytokine receptor modulators">here</a> instead)</li> <li><a href="/wiki/Glucose-6-phosphate_isomerase" title="Glucose-6-phosphate isomerase">Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)</a></li> <li><a href="/wiki/Glia_maturation_factor" title="Glia maturation factor">Glia maturation factor (GMF)</a></li> <li><a href="/wiki/Hepatoma-derived_growth_factor" title="Hepatoma-derived growth factor">Hepatoma-derived growth factor (HDGF)</a></li> <li><a href="/wiki/Interleukin" title="Interleukin">Interleukins</a>/<a href="/wiki/T-cell_growth_factor" title="T-cell growth factor">T-cell growth factors</a> (see <a href="/wiki/Template:Cytokine_receptor_modulators" title="Template:Cytokine receptor modulators">here</a> instead)</li> <li><a href="/wiki/Leukemia_inhibitory_factor" title="Leukemia inhibitory factor">Leukemia inhibitory factor (LIF)</a></li> <li><a href="/wiki/Macrophage-stimulating_protein" class="mw-redirect" title="Macrophage-stimulating protein">Macrophage-stimulating protein (MSP; HLP, HGFLP)</a></li> <li><a href="/wiki/Midkine" title="Midkine">Midkine (NEGF2)</a></li> <li><a href="/wiki/Migration-stimulating_factor" class="mw-redirect" title="Migration-stimulating factor">Migration-stimulating factor (MSF; PRG4)</a></li> <li><a href="/wiki/Oncomodulin" title="Oncomodulin">Oncomodulin</a></li> <li><a href="/wiki/Pituitary_adenylate_cyclase-activating_peptide" title="Pituitary adenylate cyclase-activating peptide">Pituitary adenylate cyclase-activating peptide (PACAP)</a></li> <li><a href="/wiki/Pleiotrophin" title="Pleiotrophin">Pleiotrophin</a></li> <li><a href="/wiki/Renalase" title="Renalase">Renalase</a></li> <li><a href="/wiki/Thrombopoietin" title="Thrombopoietin">Thrombopoietin</a> (see <a href="/wiki/Template:Cytokine_receptor_modulators" title="Template:Cytokine receptor modulators">here</a> instead)</li> <li><a href="/wiki/Wnt_signaling_pathway" title="Wnt signaling pathway">Wnt signaling proteins</a></li></ul> <ul><li><i>Additional growth factor receptor modulators:</i> <a href="/wiki/Cerebrolysin" title="Cerebrolysin">Cerebrolysin</a> (neurotrophin mixture)</li></ul> </div></td></tr></tbody></table></div> <div role="note" style="font-style: italic;">This article incorporates text from the public domain <a href="/wiki/Pfam" title="Pfam">Pfam</a> and <a href="/wiki/InterPro" title="InterPro">InterPro</a>: <a rel="nofollow" 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