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EPH receptor A3

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Target not currently curated in GtoImmuPdb

Target id: 1823

Nomenclature: EPH receptor A3

Abbreviated Name: EphA3

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 1 983 3p11.1 EPHA3 EPH receptor A3
Mouse 1 983 16 C1.3 Epha3 Eph receptor A3
Rat 1 984 11p12 Epha3 Eph receptor A3
Previous and Unofficial Names Click here for help
ETK1 | HEK | HEK4 | EK4 | EPH-like kinase 4 | ephrin type-A receptor 3 | tyrosine-protein kinase receptor REK4 | tyrosine-protein kinase TYRO4 | End3 | Mek4
Database Links Click here for help
Alphafold P29320 (Hs), P29319 (Mm), O08680 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.120.260, 2.60.40.10
ChEMBL Target CHEMBL4954 (Hs), CHEMBL2034794 (Mm)
Ensembl Gene ENSG00000044524 (Hs), ENSMUSG00000052504 (Mm), ENSRNOG00000030285 (Rn)
Entrez Gene 2042 (Hs), 13837 (Mm), 29210 (Rn)
Human Protein Atlas ENSG00000044524 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2042 (Hs), mmu:13837 (Mm), rno:29210 (Rn)
OMIM 179611 (Hs)
Pharos P29320 (Hs)
RefSeq Nucleotide NM_005233 (Hs), NM_010140 (Mm), NM_031564 (Rn)
RefSeq Protein NP_005224 (Hs), NP_034270 (Mm), NP_113752 (Rn)
SynPHARM 81491 (in complex with compound 66 [PMID: 19788238])
UniProtKB P29320 (Hs), P29319 (Mm), O08680 (Rn)
Wikipedia EPHA3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  The Human Epha3 Receptor Tyrosine Kinase and Juxtamembrane Region
PDB Id:  2GSF
Resolution:  1.77Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  Human EphA3 kinase domain in complex with compound 7
PDB Id:  4G2F
Resolution:  1.7Å
Species:  Human
References:  10
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
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 7
⤷ pIC50 9.0 (IC50 1x10-9 M) [7]
Description: In a biochemical enzyme activity assay.
compound 8h [PMID: 21561767] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pIC50 8
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [8]
compound 66 [PMID: 19788238] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 5
⤷ pIC50 7.4 (IC50 4x10-8 M) [5]
compound 20 [PMID: 23489211] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 5.6 pIC50 4
⤷ pIC50 5.6 (IC50 2.5x10-6 M) [4]
View species-specific inhibitor tables
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
fibatuzumab Peptide Primary target of this compound Hs Binding >9.0 pKd 6
⤷ pKd >9.0 (Kd <1x10-9 M) [6]
fibatuzumab Peptide Mm Binding >9.0 pKd 6
⤷ pKd >9.0 (Kd <1x10-9 M) [6]
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: 2,9
Key to terms and symbols Click column headers to sort
Target used in screen: EPHA3
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.0 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 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: 1,3
Key to terms and symbols Click column headers to sort
Target used in screen: EphA3/EPHA3
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 3.5
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 14.0 2.5 0.5
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 31.7
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 39.7 4.0 0.0
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 40.8
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.2
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 55.7 58.0 7.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 57.7
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 69.0 41.0 6.0
Akt inhibitor VIII Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 71.9 112.0 76.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Inflammation

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. 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]

3. 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]

4. 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]

5. 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]

6. Luehrsen K, Martinez D, Yi C, Bebbington CR, Yarranton GT. (2014) Antibodies to EphA3. Patent number: US8664365 B2. Assignee: Kalobios Pharmaceuticals, Inc.. Priority date: 14/08/2009. Publication date: 04/03/2014.

7. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 7 (4): 4093-109. [PMID:26675259]

8. Thomas M, Huang WS, Wen D, Zhu X, Wang Y, Metcalf CA, Liu S, Chen I, Romero J, Zou D et al.. (2011) Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett, 21 (12): 3743-8. [PMID:21561767]

9. 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]

10. Zhao H, Dong J, Lafleur K, Nevado C, Caflisch A. (2012) Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics. ACS Med Chem Lett, 3 (10): 834-8. [PMID:24900387]

How to cite this page

Type XIII RTKs: Ephrin receptor family: EPH receptor A3. Last modified on 24/04/2018. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1823.