Target Information

Target General Infomation
Target ID
T28413
Former ID
TTDI02061
Target Name
Epha3 tyrosine kinase receptor
Gene Name
EPHA3
Synonyms
EK4; EPHlike kinase 4; Ephlike tyrosine kinase 1; Ephrin typeA receptor 3; HEK; Human embryo kinase; Tyrosineprotein kinase TYRO4; Tyrosineprotein kinase receptor ETK1; hEK4; EPHA3
Target Type
Clinical Trial
Disease Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation butnot the guidance of motor and sensory axons during neuromuscular circuit development.
BioChemical Class
Kinase
UniProt ID
P29320
EC Number
EC 2.7.10.1
Sequence
MDCQLSILLLLSCSVLDSFGELIPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDE
HYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETF
NLYYMESDDDHGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFY
LAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPP
RMYCSTEGEWLVPIGKCSCNAGYEERGFMCQACRPGFYKALDGNMKCAKCPPHSSTQEDG
SMNCRCENNYFRADKDPPSMACTRPPSSPRNVISNINETSVILDWSWPLDTGGRKDVTFN
IICKKCGWNIKQCEPCSPNVRFLPRQFGLTNTTVTVTDLLAHTNYTFEIDAVNGVSELSS
PPRQFAAVSITTNQAAPSPVLTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQ
ETSYTILRARGTNVTISSLKPDTIYVFQIRARTAAGYGTNSRKFEFETSPDSFSISGESS
QVVMIAISAAVAIILLTVVIYVLIGRFCGYKSKHGADEKRLHFGNGHLKLPGLRTYVDPH
TYEDPTQAVHEFAKELDATNISIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYT
EKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTV
IQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT
TRGGKIPIRWTSPEAIAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEG
YRLPPPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSN
LLLDQSNVDITTFRTTGDWLNGVWTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVG
PQKKIISSIKALETQSKNGPVPV
Drugs and Mode of Action
Drug(s) KB-004 Drug Info Phase 1/2 Hematological malignancies [523188]
Inhibitor compound 20 Drug Info [532265]
compound 66 Drug Info [530413]
compound 8h Drug Info [531471]
Pathways
KEGG Pathway Axon guidance
Pathway Interaction Database EphrinA-EPHA pathway
EPHA forward signaling
Reactome EPH-Ephrin signaling
EPHA-mediated growth cone collapse
EPH-ephrin mediated repulsion of cells
WikiPathways NRF2 pathway
References
Ref 523188ClinicalTrials.gov (NCT01211691) Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF). U.S. National Institutes of Health.
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 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 532265Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
Ref 549957Clinical pipeline report, company report or official report of Kalobios.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.