Target General Infomation
Target ID
T57278
Former ID
TTDR01214
Target Name
Ephrin type-A receptor 2
Gene Name
EPHA2
Synonyms
EphA2receptor; Epithelial cell kinase; Tyrosine-protein kinase receptor ECK; EPHA2
Target Type
Clinical Trial
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.
BioChemical Class
Kinase
UniProt ID
EC Number
EC 2.7.10.1
Sequence
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMN
DMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFN
LYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYL
AFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGG
EEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPS
PEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDI
VYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSG
LVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSN
SYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGG
VAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQA
VLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDF
LGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGML
RGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIP
IRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPM
DCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSG
SEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAY
SLLGLKDQVNTVGIPI
Drugs and Mode of Action
Drug(s) DS-8895 Drug Info Phase 1 Solid tumours [524936]
MEDI-547 Drug Info Phase 1 Solid tumours [522493]
MEDI-543 Drug Info Preclinical Cancer [547468]
Inhibitor compound 20 Drug Info [532265]
compound 66 Drug Info [530413]
compound 8h Drug Info [531471]
Phosphoaminophosphonic Acid-Adenylate Ester Drug Info [551374]
Modulator EphA2-targeting BiTE molecules Drug Info [543506]
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 522493ClinicalTrials.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 524936ClinicalTrials.gov (NCT02252211) Safety and Bio-Imaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers. U.S. National Institutes of Health.
Ref 547468Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016645)
Ref 530413Structure-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 531219Clinical and biological impact of EphA2 overexpression and angiogenesis in endometrial cancer. Cancer Biol Ther. 2010 Dec 15;10(12):1306-14. Epub 2010 Dec 15.
Ref 531471Discovery 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 531635Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
Ref 532265Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
Ref 543506(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).
Ref 550589Clinical pipeline report, company report or official report of Daiichi Sankyo.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

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