Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T49507
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| Former ID |
TTDC00045
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| Target Name |
Ephrin type-B receptor 4
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| Gene Name |
EPHB4
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| Synonyms |
Tyrosine-protein kinase TYRO11; Tyrosine-protein kinase receptor HTK; EPHB4
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| Target Type |
Clinical Trial
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| Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
| Late-stage non-small cell lung cancer [ICD9: 162, 203.0, 208.9; ICD10: C33-C34] | |||||
| Function |
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor isreferred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4- mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis.
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| BioChemical Class |
Kinase
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| Target Validation |
T49507
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| UniProt ID | |||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MELRVLLCWASLAAALEETLLNTKLETADLKWVTFPQVDGQWEELSGLDEEQHSVRTYEV
CDVQRAPGQAHWLRTGWVPRRGAVHVYATLRFTMLECLSLPRAGRSCKETFTVFYYESDA DTATALTPAWMENPYIKVDTVAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYLAFQD QGACMALLSLHLFYKKCAQLTVNLTRFPETVPRELVVPVAGSCVVDAVPAPGPSPSLYCR EDGQWAEQPVTGCSCAPGFEAAEGNTKCRACAQGTFKPLSGEGSCQPCPANSHSNTIGSA VCQCRVGYFRARTDPRGAPCTTPPSAPRSVVSRLNGSSLHLEWSAPLESGGREDLTYALR CRECRPGGSCAPCGGDLTFDPGPRDLVEPWVVVRGLRPDFTYTFEVTALNGVSSLATGPV PFEPVNVTTDREVPPAVSDIRVTRSSPSSLSLAWAVPRAPSGAVLDYEVKYHEKGAEGPS SVRFLKTSENRAELRGLKRGASYLVQVRARSEAGYGPFGQEHHSQTQLDESEGWREQLAL IAGTAVVGVVLVLVVIVVAVLCLRKQSNGREAEYSDKHGQYLIGHGTKVYIDPFTYEDPN EAVREFAKEIDVSYVKIEEVIGAGEFGEVCRGRLKAPGKKESCVAIKTLKGGYTERQRRE FLSEASIMGQFEHPNIIRLEGVVTNSMPVMILTEFMENGALDSFLRLNDGQFTVIQLVGM LRGIASGMRYLAEMSYVHRDLAARNILVNSNLVCKVSDFGLSRFLEENSSDPTYTSSLGG KIPIRWTAPEAIAFRKFTSASDAWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLP PPPDCPTSLHQLMLDCWQKDRNARPRFPQVVSALDKMIRNPASLKIVARENGGASHPLLD QRQPHYSAFGSVGEWLRAIKMGRYEESFAAAGFGSFELVSQISAEDLLRIGVTLAGHQKK ILASVQHMKSQAKPGTPGGTGGPAPQY |
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| Drugs and Mode of Action | |||||
| Drug(s) | KD019 | Drug Info | Phase 2 | Late-stage non-small cell lung cancer | [1] |
| Inhibitor | compound 20 | Drug Info | [2] | ||
| compound 66 | Drug Info | [3] | |||
| EphB4 inhibitors | Drug Info | [4] | |||
| TG-100435 | Drug Info | [5] | |||
| Modulator | KD019 | Drug Info | [6], [7] | ||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| KEGG Pathway | Axon guidance | ||||
| Pathway Interaction Database | EPHB forward signaling | ||||
| EphrinB-EPHB pathway | |||||
| Ephrin B reverse signaling | |||||
| Reactome | EPH-Ephrin signaling | ||||
| EPHB-mediated forward signaling | |||||
| EPH-ephrin mediated repulsion of cells | |||||
| WikiPathways | Vitamin D Receptor Pathway | ||||
| References | |||||
| REF 1 | ClinicalTrials.gov (NCT01487174) KD019 Versus Erlotinib in Subjects With Stage IIIB/IV Non Small Cell Lung Cancer With Progression After First- or Second-Line Chemotherapy. U.S. National Institutes of Health. | ||||
| REF 2 | Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47. | ||||
| REF 3 | Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46. | ||||
| REF 4 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1833). | ||||
| REF 5 | Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. Epub 2006 Nov 7.Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays. | ||||
| REF 6 | XL647--a multitargeted tyrosine kinase inhibitor: results of a phase II study in subjects with non-small cell lung cancer who have progressed after responding to treatment with either gefitinib or erlotinib. J Thorac Oncol. 2012 Jan;7(1):219-26. | ||||
| REF 7 | Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65. doi: 10.1097/JTO.0b013e31824c943f. | ||||
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