Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8MDAC)

• DTT Name: Ephrin type-B receptor 1 (EPHB1)
• Synonyms: hEK6; Tyrosine-protein kinase receptor EPH-2; Neuronally-expressed EPH-related tyrosine kinase; EPHT2; EPH-like kinase 6; EPH tyrosine kinase 2; ELK; EK6
• Gene Name: EPHB1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: EPHB1_HUMAN
• TTD ID: T02446
• EC Number: EC 2.7.10.1
• Sequence:
  MALDYLLLLLLASAVAAMEETLMDTRTATAELGWTANPASGWEEVSGYDENLNTIRTYQV
  CNVFEPNQNNWLLTTFINRRGAHRIYTEMRFTVRDCSSLPNVPGSCKETFNLYYYETDSV
  IATKKSAFWSEAPYLKVDTIAADESFSQVDFGGRLMKVNTEVRSFGPLTRNGFYLAFQDY
  GACMSLLSVRVFFKKCPSIVQNFAVFPETMTGAESTSLVIARGTCIPNAEEVDVPIKLYC
  NGDGEWMVPIGRCTCKPGYEPENSVACKACPAGTFKASQEAEGCSHCPSNSRSPAEASPI
  CTCRTGYYRADFDPPEVACTSVPSGPRNVISIVNETSIILEWHPPRETGGRDDVTYNIIC
  KKCRADRRSCSRCDDNVEFVPRQLGLTECRVSISSLWAHTPYTFDIQAINGVSSKSPFPP
  QHVSVNITTNQAAPSTVPIMHQVSATMRSITLSWPQPEQPNGIILDYEIRYYEKEHNEFN
  SSMARSQTNTARIDGLRPGMVYVVQVRARTVAGYGKFSGKMCFQTLTDDDYKSELREQLP
  LIAGSAAAGVVFVVSLVAISIVCSRKRAYSKEAVYSDKLQHYSTGRGSPGMKIYIDPFTY
  EDPNEAVREFAKEIDVSFVKIEEVIGAGEFGEVYKGRLKLPGKREIYVAIKTLKAGYSEK
  QRRDFLSEASIMGQFDHPNIIRLEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQ
  LVGMLRGIAAGMKYLAEMNYVHRDLAARNILVNSNLVCKVSDFGLSRYLQDDTSDPTYTS
  SLGGKIPVRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQD
  YRLPPPMDCPAALHQLMLDCWQKDRNSRPRFAEIVNTLDKMIRNPASLKTVATITAVPSQ
  PLLDRSIPDFTAFTTVDDWLSAIKMVQYRDSFLTAGFTSLQLVTQMTSEDLLRIGITLAG
  HQKKILNSIHSMRVQISQSPTAMA
• 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation. Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway:
  EPHB-mediated forward signaling (R-HSA-3928662)
  Ephrin signaling (R-HSA-3928664)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  EPH-Ephrin signaling (R-HSA-2682334)

Molecular Interaction Atlas (MIA) of This DTT

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID19788238C66	DMCVJK9	Discovery agent	N.A.	Investigative	[1]
PMID23489211C20	DMDYC4J	Discovery agent	N.A.	Investigative	[2]

References

• [1] 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.
• [2] Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.