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EPH receptor B2

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Target id: 1831

Nomenclature: EPH receptor B2

Abbreviated Name: EphB2

Family: Type XIII RTKs: Ephrin receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1055 1p36.12 EPHB2 EPH receptor B2
Mouse 1 986 4 69.0 cM Ephb2 Eph receptor B2
Rat - 986 5q36 Ephb2 Eph receptor B2
Previous and Unofficial Names Click here for help
DRT | EPHT3 | Tyro5 | ephrin type-B receptor 2 | Neural kinase | Nuk receptor tyrosine kinase | tyrosine-protein kinase receptor EPH-3 | eteck | Nuk | Prkm5 | Sek3 | tyrosine-protein kinase receptor SEK-3
Database Links Click here for help
Alphafold P29323 (Hs), P54763 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10, 2.60.120.260
ChEMBL Target CHEMBL3290 (Hs), CHEMBL5961 (Mm)
Ensembl Gene ENSG00000133216 (Hs), ENSMUSG00000028664 (Mm), ENSRNOG00000012531 (Rn)
Entrez Gene 2048 (Hs), 13844 (Mm), 313633 (Rn)
Human Protein Atlas ENSG00000133216 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2048 (Hs), mmu:13844 (Mm), rno:313633 (Rn)
OMIM 600997 (Hs)
Orphanet ORPHA121567 (Hs)
Pharos P29323 (Hs)
RefSeq Nucleotide NM_004442 (Hs), NM_010142 (Mm), NM_001127319 (Rn)
RefSeq Protein NP_004433 (Hs), NP_034272 (Mm), NP_001120791 (Rn)
UniProtKB P29323 (Hs), P54763 (Mm)
Wikipedia EPHB2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  EphB2/SNEW Antagonistic Peptide Complex
PDB Id:  2QBX
Resolution:  2.3Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Eph A4 receptor
PDB Id:  3CKH
Resolution:  2.8Å
Species:  Human
References:  8
Enzyme Reaction Click here for help
EC Number: 2.7.10.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
DDR1/2 inhibitor 5n Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pKd 9
⤷ pKd 6.6 (Kd 2.6x10-7 M) [9]
compound 66 [PMID: 19788238] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 7
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [7]
RIPK3 inhibitor 18 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 5
⤷ pIC50 8.0 (IC50 1x10-8 M) [5]
compound 20 [PMID: 23489211] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 5.4 pIC50 6
⤷ pIC50 5.4 (IC50 3.8x10-6 M) [6]
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,10
Key to terms and symbols Click column headers to sort
Target used in screen: EPHB2
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.4 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
doramapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: EphB2/EPHB2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition -0.2
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 1.5
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 17.4
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 24.4
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.6 21.5 0.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 33.6 25.0 0.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 40.7 4.0 -1.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.6 3.0 -1.0
JAK3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 66.1 65.0 1.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 72.1
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Prostate cancer/brain cancer susceptibility
OMIM: 603688
Orphanet: ORPHA1331

References

Show »

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Chrencik JE, Brooun A, Recht MI, Nicola G, Davis LK, Abagyan R, Widmer H, Pasquale EB, Kuhn P. (2007) Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition. J Biol Chem, 282 (50): 36505-13. [PMID:17897949]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

5. Hart AC, Abell L, Guo J, Mertzman ME, Padmanabha R, Macor JE, Chaudhry C, Lu H, O'Malley K, Shaw PJ et al.. (2019) Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. ACS Med Chem Lett, Article ASAP. DOI: 10.1021/acsmedchemlett.9b00065

6. Incerti M, Tognolini M, Russo S, Pala D, Giorgio C, Hassan-Mohamed I, Noberini R, Pasquale EB, Vicini P, Piersanti S et al.. (2013) Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem, 56 (7): 2936-47. [PMID:23489211]

7. Lafleur K, Huang D, Zhou T, Caflisch A, Nevado C. (2009) Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem, 52 (20): 6433-46. [PMID:19788238]

8. Qin H, Shi J, Noberini R, Pasquale EB, Song J. (2008) Crystal structure and NMR binding reveal that two small molecule antagonists target the high affinity ephrin-binding channel of the EphA4 receptor. J Biol Chem, 283 (43): 29473-84. [PMID:18708347]

9. Wang Z, Zhang Y, Pinkas DM, Fox AE, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q et al.. (2018) Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2. J Med Chem, 61 (17): 7977-7990. [PMID:30075624]

10. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Type XIII RTKs: Ephrin receptor family: EPH receptor B2. Last modified on 17/05/2019. Accessed on 04/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1831.