Target Information
Target General Infomation | |||||
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Target ID |
T57278
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Former ID |
TTDR01214
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Target Name |
Ephrin type-A receptor 2
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Gene Name |
EPHA2
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Synonyms |
EphA2receptor; Epithelial cell kinase; Tyrosine-protein kinase receptor ECK; EPHA2
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Target Type |
Clinical Trial
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.
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BioChemical Class |
Kinase
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UniProt ID | |||||
EC Number |
EC 2.7.10.1
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Sequence |
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMN
DMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFN LYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYL AFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGG EEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPS PEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDI VYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSG LVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSN SYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGG VAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQA VLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDF LGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGML RGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIP IRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPM DCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSG SEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAY SLLGLKDQVNTVGIPI |
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Drugs and Mode of Action | |||||
Drug(s) | DS-8895 | Drug Info | Phase 1 | Solid tumours | [1] |
MEDI-547 | Drug Info | Phase 1 | Solid tumours | [2] | |
MEDI-543 | Drug Info | Preclinical | Cancer | [3] | |
Inhibitor | compound 20 | Drug Info | [4] | ||
compound 66 | Drug Info | [5] | |||
compound 8h | Drug Info | [6] | |||
Phosphoaminophosphonic Acid-Adenylate Ester | Drug Info | [7] | |||
Modulator | EphA2-targeting BiTE molecules | Drug Info | [8] | ||
Pathways | |||||
KEGG Pathway | Ras signaling pathway | ||||
Rap1 signaling pathway | |||||
PI3K-Akt signaling pathway | |||||
Axon guidance | |||||
NetPath Pathway | TGF_beta_Receptor Signaling Pathway | ||||
Pathway Interaction Database | EphrinA-EPHA pathway | ||||
Arf6 signaling events | |||||
Direct p53 effectors | |||||
EPHA forward signaling | |||||
Stabilization and expansion of the E-cadherin adherens junction | |||||
EPHA2 forward signaling | |||||
Reactome | EPH-Ephrin signaling | ||||
EPHA-mediated growth cone collapse | |||||
EPH-ephrin mediated repulsion of cells | |||||
WikiPathways | NRF2 pathway | ||||
References | |||||
REF 1 | ClinicalTrials.gov (NCT02252211) Safety and Bio-Imaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers. U.S. National Institutes of Health. | ||||
REF 2 | ClinicalTrials.gov (NCT00796055) Study of MEDI-547 to Evaluate the Safety, Tolerability, and Biologic Activity of IV Administration in Subjects With Relapsed or Refractory Solid Tumors. U.S. NationalInstitutes of Health. | ||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016645) | ||||
REF 4 | Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47. | ||||
REF 5 | 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 6 | Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8. | ||||
REF 7 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | ||||
REF 8 | (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: 1822). |
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