FGR proto-oncogene, Src family tyrosine kinase | Src family | IUPHAR/BPS Guide to PHARMACOLOGY

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FGR proto-oncogene, Src family tyrosine kinase

target has curated data in GtoImmuPdb

Target id: 2024

Nomenclature: FGR proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Fgr

Family: Src 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 - 529 1p36.2-p36.1 FGR FGR proto-oncogene, Src family tyrosine kinase
Mouse - 517 4 D2.3 Fgr FGR proto-oncogene
Rat - 517 5 q36 Fgr FGR proto-oncogene
Previous and Unofficial Names
c-fgr | SRC2 | feline Gardner-Rasheed sarcoma viral oncogene homolog | feline Gardner-Rasheed sarcoma viral oncogene | FGR proto-oncogene
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.10.2

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 Affinity Parameter Reference
eCF506 Hs Inhibition >9.3 pIC50 6
pIC50 >9.3 (IC50 <5x10-10 M) [6]
compound 2 [PMID: 15546730] Hs Inhibition >9.0 pIC50 3
pIC50 >9.0 (IC50 <1x10-9 M) [3]
compound 2c [PMID: 24900538] Hs Inhibition 8.7 pIC50 10
pIC50 8.7 (IC50 2.2x10-9 M) [10]
P505-15 Hs Inhibition 7.1 pIC50 4
pIC50 7.1 (IC50 8.1x10-8 M) [4]
apitolisib Hs Inhibition 6.2 pIC50 9
pIC50 6.2 (IC50 6.97x10-7 M) [9]
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: 5,11

Key to terms and symbols Click column headers to sort
Target used in screen: FGR
Ligand Sp. Type Action Affinity Parameter
dasatinib Hs Inhibitor Inhibition 9.3 pKd
PD-173955 Hs Inhibitor Inhibition 8.6 pKd
bosutinib Hs Inhibitor Inhibition 8.2 pKd
staurosporine Hs Inhibitor Inhibition 7.8 pKd
tamatinib Hs Inhibitor Inhibition 7.5 pKd
foretinib Hs Inhibitor Inhibition 7.4 pKd
lestaurtinib Hs Inhibitor Inhibition 7.3 pKd
PLX-4720 Hs Inhibitor Inhibition 7.2 pKd
fedratinib Hs Inhibitor Inhibition 7.1 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.9 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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: Fgr/FGR
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.3 0.5 1.0
dasatinib Hs Inhibitor Inhibition 1.7
Lck inhibitor Hs Inhibitor Inhibition 2.9 2.0 0.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 3.0 1.0 2.0
TWS119 Hs Inhibitor Inhibition 5.3 0.0 2.0
dovitinib Hs Inhibitor Inhibition 6.3
Src kinase inhibitor I Hs Inhibitor Inhibition 8.9 7.0 2.0
bosutinib Hs Inhibitor Inhibition 11.5
SU11652 Hs Inhibitor Inhibition 11.5 8.0 2.0
indirubin derivative E804 Hs Inhibitor Inhibition 11.6 3.0 3.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [2].
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  8
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Primarily in mantle zone B cells,
References:  8
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
neutrophil (CL:0000775)
References:  8
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
References:  8
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 6 GO processes
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0043306 positive regulation of mast cell degranulation ISS
GO:0043312 neutrophil degranulation TAS
GO:0045087 innate immune response IBA
GO:0045088 regulation of innate immune response ISS
GO:0050764 regulation of phagocytosis ISS
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0050764 regulation of phagocytosis ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0002768 immune response-regulating cell surface receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0043306 positive regulation of mast cell degranulation ISS
GO:0045088 regulation of innate immune response ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0050715 positive regulation of cytokine secretion ISS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0002768 immune response-regulating cell surface receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0043306 positive regulation of mast cell degranulation ISS
GO:0043312 neutrophil degranulation TAS

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. Baruzzi A, Iacobucci I, Soverini S, Lowell CA, Martinelli G, Berton G. (2010) c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration. FEBS Lett., 584 (1): 15-21. [PMID:19903482]

3. Chen P, Norris D, Das J, Spergel SH, Wityak J, Leith L, Zhao R, Chen BC, Pitt S, Pang S et al.. (2004) Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg. Med. Chem. Lett., 14 (24): 6061-6. [PMID:15546730]

4. Coffey G, DeGuzman F, Inagaki M, Pak Y, Delaney SM, Ives D, Betz A, Jia ZJ, Pandey A, Baker D et al.. (2012) Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J. Pharmacol. Exp. Ther., 340 (2): 350-9. [PMID:22040680]

5. 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]

6. Fraser C, Dawson JC, Dowling R, Houston DR, Weiss JT, Munro AF, Muir M, Harrington L, Webster SP, Frame MC et al.. (2016) Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J. Med. Chem., 59 (10): 4697-710. [PMID:27115835]

7. 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]

8. Lowell CA. (2004) Src-family kinases: rheostats of immune cell signaling. Mol. Immunol., 41 (6-7): 631-43. [PMID:15220000]

9. Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J et al.. (2011) Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer. J. Med. Chem., 54 (21): 7579-87. [PMID:21981714]

10. Wang T, Lamb ML, Block MH, Davies AM, Han Y, Hoffmann E, Ioannidis S, Josey JA, Liu ZY, Lyne PD et al.. (2012) Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett, 3 (9): 705-9. [PMID:24900538]

11. 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

Src family: FGR proto-oncogene, Src family tyrosine kinase. Last modified on 16/05/2017. Accessed on 23/04/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2024.