General Information of Drug Therapeutic Target (DTT) (ID: TTRJB2G)

DTT Name Ephrin type-A receptor 2 (EPHA2)
Synonyms Tyrosine-protein kinase receptor ECK; Epithelial cell kinase; EphA2receptor; ECK
Gene Name EPHA2
DTT Type
Clinical trial target
[1]
BioChemical Class
Kinase
UniProt ID
EPHA2_HUMAN
TTD ID
T57278
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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
Function
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. 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.
KEGG Pathway
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
PI3K-Akt signaling pathway (hsa04151 )
Axon guidance (hsa04360 )
Reactome Pathway
EPHA-mediated growth cone collapse (R-HSA-3928663 )
EPH-ephrin mediated repulsion of cells (R-HSA-3928665 )
EPH-Ephrin signaling (R-HSA-2682334 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
BT5528 DMYBKMV Solid tumour/cancer 2A00-2F9Z Phase 1/2 [2]
CAR-T cells targeting EphA2 DMN3C2I Malignant glioma 2A00.0 Phase 1/2 [1]
DS-8895 DM31VNC Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MEDI-547 DM3WP70 Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
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1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
MEDI-543 DM7Q1PF Solid tumour/cancer 2A00-2F9Z Preclinical [5]
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4 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AMP-PNP DMTOK1D Discovery agent N.A. Investigative [6]
PMID19788238C66 DMCVJK9 Discovery agent N.A. Investigative [7]
PMID21561767C8h DMABZH6 Discovery agent N.A. Investigative [8]
PMID23489211C20 DMDYC4J Discovery agent N.A. Investigative [9]
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References

1 ClinicalTrials.gov (NCT02575261) CAR-T Cell Immunotherapy for EphA2 Positive Malignant Glioma Patients
2 MMAE Delivery Using the Bicycle Toxin Conjugate BT5528. Mol Cancer Ther. 2020 Jul;19(7):1385-1394.
3 Clinical pipeline report, company report or official report of Daiichi Sankyo.
4 URL: 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).
5 Clinical and biological impact of EphA2 overexpression and angiogenesis in endometrial cancer. Cancer Biol Ther. 2010 Dec 15;10(12):1306-14.
6 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
7 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.
8 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.
9 Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.