Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKPV6O)

• DTT Name: Ephrin type-B receptor 2 (EPHB2)
• Synonyms: hEK5; Tyrosine-protein kinase receptor EPH-3; Tyrosine-protein kinase TYRO5; TYRO5; Renal carcinoma antigen NY-REN-47; Receptor protein-tyrosine kinase HEK5; EphB2 receptor tyrosine kinase; EphB2; EPTH3; EPHT3; EPH-like kinase 5; EPH tyrosine kinase 3; ELK-related tyrosine kinase; EK5; Developmentally-regulated Eph-related tyrosine kinase; DRT
• Gene Name: EPHB2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: EPHB2_HUMAN
• TTD ID: T73756
• EC Number: EC 2.7.10.1
• Sequence:
  MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQ
  VCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADF
  DSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQD
  YGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLY
  CNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA
  TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSGGREDLVYNI
  ICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAVNGVTDQSPF
  SPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSE
  YNATAIKSPTNTVTVQGLKAGAIYVFQVRARTVAGYGRYSGKMYFQTMTEAEYQTSIQEK
  LPLIIGSSAAGLVFLIAVVVIAIVCNRRGFERADSEYTDKLQHYTSGHMTPGMKIYIDPF
  TYEDPNEAVREFAKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYT
  EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTV
  IQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY
  TSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIE
  QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRNPNSLKAMAPLSSGI
  NLPLLDRTIPDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTL
  AGHQKKILNSIQVMRAQMNQIQSVEGQPLARRPRATGRTKRCQPRDVTKKTCNSNDGKKK
  GMGKKKTDPGRGREIQGIFFKEDSHKESNDCSCGG
• 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. 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:
  L1CAM interactions (R-HSA-373760)
  EPHB-mediated forward signaling (R-HSA-3928662)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  EPH-Ephrin signaling (R-HSA-2682334)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BVD-523	DMNB4XK	Melanoma	2C30	Phase 2	[1]
SEphB4-HSA	DMD8RU0	Kaposi sarcoma	2B57	Phase 2	[2]
KO-947	DMZMSBI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]
MK-8353	DMLCTI5	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

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	[3]
PMID19788238C66	DMCVJK9	Discovery agent	N.A.	Investigative	[4]
PMID23489211C20	DMDYC4J	Discovery agent	N.A.	Investigative	[5]
SNEWIQPRLPQH	DMYUH62	Discovery agent	N.A.	Investigative	[6]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] National Cancer Institute Drug Dictionary (drug name SEphB4-HSA).
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] 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.
• [5] Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
• [6] Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition. J Biol Chem. 2007 Dec 14;282(50):36505-13.