Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Ephrin type-A receptor 1 (EPHA1)
• Synonyms: hEpha1; Tyrosine-protein kinase receptor EPH; Erythropoietin-producing hepatoma receptor; EPHT1; EPHT; EPH tyrosine kinase 1; EPH tyrosine kinase; EPH
• Gene Name: EPHA1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: EPHA1_HUMAN
• TTD ID: T28418
• EC Number: EC 2.7.10.1
• Sequence:
  MERRWPLGLGLVLLLCAPLPPGARAKEVTLMDTSKAQGELGWLLDPPKDGWSEQQQILNG
  TPLYMYQDCPMQGRRDTDHWLRSNWIYRGEEASRVHVELQFTVRDCKSFPGGAGPLGCKE
  TFNLLYMESDQDVGIQLRRPLFQKVTTVAADQSFTIRDLVSGSVKLNVERCSLGRLTRRG
  LYLAFHNPGACVALVSVRVFYQRCPETLNGLAQFPDTLPGPAGLVEVAGTCLPHARASPR
  PSGAPRMHCSPDGEWLVPVGRCHCEPGYEEGGSGEACVACPSGSYRMDMDTPHCLTCPQQ
  STAESEGATICTCESGHYRAPGEGPQVACTGPPSAPRNLSFSASGTQLSLRWEPPADTGG
  RQDVRYSVRCSQCQGTAQDGGPCQPCGVGVHFSPGARGLTTPAVHVNGLEPYANYTFNVE
  AQNGVSGLGSSGHASTSVSISMGHAESLSGLSLRLVKKEPRQLELTWAGSRPRSPGANLT
  YELHVLNQDEERYQMVLEPRVLLTELQPDTTYIVRVRMLTPLGPGPFSPDHEFRTSPPVS
  RGLTGGEIVAVIFGLLLGAALLLGILVFRSRRAQRQRQQRQRDRATDVDREDKLWLKPYV
  DLQAYEDPAQGALDFTRELDPAWLMVDTVIGEGEFGEVYRGTLRLPSQDCKTVAIKTLKD
  TSPGGQWWNFLREATIMGQFSHPHILHLEGVVTKRKPIMIITEFMENGALDAFLREREDQ
  LVPGQLVAMLQGIASGMNYLSNHNYVHRDLAARNILVNQNLCCKVSDFGLTRLLDDFDGT
  YETQGGKIPIRWTAPEAIAHRIFTTASDVWSFGIVMWEVLSFGDKPYGEMSNQEVMKSIE
  DGYRLPPPVDCPAPLYELMKNCWAYDRARRPHFQKLQAHLEQLLANPHSLRTIANFDPRM
  TLRLPSLSGSDGIPYRTVSEWLESIRMKRYILHFHSAGLDTMECVLELTAEDLTQMGITL
  PGHQKRILCSIQGFKD
• 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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. 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.
• Reactome Pathway:
  POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247)
  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

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.