EPH receptor A3 | Type XIII RTKs: Ephrin receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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EPH receptor A3

Target not currently curated in GtoImmuPdb

Target id: 1823

Nomenclature: EPH receptor A3

Abbreviated Name: EphA3

Family: Type XIII RTKs: Ephrin receptor family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 983 3p11.2 EPHA3 EPH receptor A3
Mouse 1 984 16 Epha3 Eph receptor A3
Rat 1 984 11p12 Epha3 Eph receptor A3
Previous and Unofficial Names
HEK | HEK4 | ETK1 | EK4 | EPH-like kinase 4 | ephrin type-A receptor 3 | tyrosine-protein kinase receptor REK4 | tyrosine-protein kinase TYRO4 | End3 | Mek4
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.10.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sitravatinib 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] Hs Inhibition 8.9 pIC50 8
pIC50 8.9 (IC50 1.2x10-9 M) [8]
compound 66 [PMID: 19788238] Hs Inhibition 7.4 pIC50 5
pIC50 7.4 (IC50 4x10-8 M) [5]
compound 20 [PMID: 23489211] 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 Hs Binding >9.0 pKd 6
pKd >9.0 (Kd <1x10-9 M) [6]
fibatuzumab Mm Binding >9.0 pKd 6
pKd >9.0 (Kd <1x10-9 M) [6]
DiscoveRx KINOMEscan® screen
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 Hs Inhibitor Inhibition 10.0 pKd
foretinib Hs Inhibitor Inhibition 9.0 pKd
bosutinib Hs Inhibitor Inhibition 8.2 pKd
PD-173955 Hs Inhibitor Inhibition 8.1 pKd
staurosporine Hs Inhibitor Inhibition 7.6 pKd
AST-487 Hs Inhibitor Inhibition 7.1 pKd
nilotinib Hs Inhibitor Inhibition 7.0 pKd
lestaurtinib Hs Inhibitor Inhibition 6.8 pKd
tamatinib Hs Inhibitor Inhibition 6.4 pKd
PP-242 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
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 Hs Inhibitor Inhibition 3.5
staurosporine Hs Inhibitor Inhibition 14.0 2.5 0.5
bosutinib Hs Inhibitor Inhibition 31.7
TWS119 Hs Inhibitor Inhibition 39.7 4.0 0.0
nilotinib Hs Inhibitor Inhibition 40.8
tozasertib Hs Inhibitor Inhibition 44.2
dorsomorphin Hs Inhibitor Inhibition 55.7 58.0 7.0
vandetanib Hs Inhibitor Inhibition 57.7
indirubin derivative E804 Hs Inhibitor Inhibition 69.0 41.0 6.0
Akt inhibitor VIII 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
GO Annotations:  Associated to 1 GO processes
GO:0045806 negative regulation of endocytosis IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0034097 response to cytokine IEP
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0001660 fever generation IEP

References

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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 29/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1823.