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FGR proto-oncogene, Src family tyrosine kinase

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2024

Nomenclature: FGR proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Fgr

Family: Src family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 529 1p35.3 FGR FGR proto-oncogene, Src family tyrosine kinase
Mouse - 517 4 D2.3 Fgr FGR proto-oncogene, Src family tyrosine kinase
Rat - 517 5q36 Fgr FGR proto-oncogene, Src family tyrosine kinase
Previous and Unofficial Names Click here for help
c-fgr | SRC2 | feline Gardner-Rasheed sarcoma viral oncogene homolog | feline Gardner-Rasheed sarcoma viral oncogene | FGR proto-oncogene
Database Links Click here for help
Alphafold P09769 (Hs), P14234 (Mm), Q6P6U0 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 3.30.505.10
ChEMBL Target CHEMBL4454 (Hs), CHEMBL2034795 (Mm), CHEMBL4362 (Rn)
Ensembl Gene ENSG00000000938 (Hs), ENSMUSG00000028874 (Mm), ENSRNOG00000009912 (Rn)
Entrez Gene 2268 (Hs), 14191 (Mm), 79113 (Rn)
Human Protein Atlas ENSG00000000938 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:2268 (Hs), mmu:14191 (Mm), rno:79113 (Rn)
OMIM 164940 (Hs)
Pharos P09769 (Hs)
RefSeq Nucleotide NM_001042729 (Hs), NM_010208 (Mm), NM_024145 (Rn)
RefSeq Protein NP_001036194 (Hs), NP_034338 (Mm), NP_077059 (Rn)
UniProtKB P09769 (Hs), P14234 (Mm), Q6P6U0 (Rn)
Wikipedia FGR (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

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
eCF506 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.3 pIC50 6
⤷ pIC50 >9.3 (IC50 <5x10-10 M) [6]
compound 2 [PMID: 15546730] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >9.0 pIC50 3
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [3]
compound 2c [PMID: 24900538] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 11
⤷ pIC50 8.7 (IC50 2.2x10-9 M) [11]
RIPK3 inhibitor 18 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 8
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [8]
P505-15 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 4
⤷ pIC50 7.1 (IC50 8.1x10-8 M) [4]
apitolisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 10
⤷ pIC50 6.2 (IC50 6.97x10-7 M) [10]
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: 5,12
Key to terms and symbols Click column headers to sort
Target used in screen: FGR
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.3 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure 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 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: 1,7
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.3 0.5 1.0
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.7
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.9 2.0 0.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 3.0 1.0 2.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 5.3 0.0 2.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.3
Src kinase inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 7.0 2.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 11.5
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.5 8.0 2.0
indirubin derivative E804 Small molecule or natural product 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:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Primarily in mantle zone B cells,
References:  9
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
neutrophil (CL:0000775)
References:  9
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
References:  9
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  9
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling

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. 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. 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

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

10. 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]

11. 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]

12. 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 17/05/2019. Accessed on 04/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2024.