fibroblast growth factor receptor 2

Target id: 1809

Nomenclature: fibroblast growth factor receptor 2

Abbreviated Name: FGFR2

Family: Type V RTKs: FGF (fibroblast growth factor) 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 1 821 10q25.3-q26 FGFR2 fibroblast growth factor receptor 2
Mouse 1 840 7 Fgfr2 fibroblast growth factor receptor 2
Rat - 841 1q37 Fgfr2 fibroblast growth factor receptor 2
Previous and Unofficial Names
bacteria-expressed kinase
craniofacial dysostosis 1
Crouzon syndrome
Jackson-Weiss syndrome
keratinocyte growth factor receptor
Pfeiffer syndrome
Fgfr7
BEK
CD332
CEK3
CFD1
ECT1
JWS
KGFR
TK14
TK25
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Enzyme
KEGG Gene
NeXtProt
OMIM
Orphanet
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Tyrosine Phosphorylated Activated FGF Receptor 2 (FGFR2) Kinase Domain in Complex with ATP Analog and Substrate Peptide
PDB Id:  2PVF
Resolution:  1.8Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
FGF-1 (FGF1, P05230) > FGF-4 (FGF4, P08620), FGF-7 (FGF7, P21781), FGF-9 (FGF9, P31371) > FGF-2 (FGF2, P09038), FGF-6 (FGF6, P10767)  [8]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BGJ-398 Hs Inhibition 8.85 pIC50 6
pIC50 8.85 (IC50 1.4x10-9 M) [6]
LY2874455 Hs Inhibition 8.59 pIC50 11
pIC50 8.59 (IC50 2.6x10-9 M) [11]
AZD4547 Hs Inhibition >8.3 pIC50 2
pIC50 >8.3 (IC50 <5x10-9 M) [2]
nintedanib Hs Inhibition 7.43 pIC50 7
pIC50 7.43 (IC50 3.7x10-8 M) [7]
MK-2461 Hs Inhibition 7.41 pIC50 9
pIC50 7.41 (IC50 3.9x10-8 M) [9]
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
palifermin Hs Agonist - -
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: 4,10

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR2
Ligand Sp. Type Action Affinity Units
PD-173955 Hs Inhibitor Inhibition 7.51 pKd
cediranib Hs Inhibitor Inhibition 7.46 pKd
tamatinib Hs Inhibitor Inhibition 7.14 pKd
staurosporine Hs Inhibitor Inhibition 7.0 pKd
brivanib Hs Inhibitor Inhibition 6.96 pKd
axitinib Hs Inhibitor Inhibition 6.96 pKd
pazopanib Hs Inhibitor Inhibition 6.68 pKd
PP-242 Hs Inhibitor Inhibition 6.68 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.6 pKd
dovitinib Hs Inhibitor Inhibition 6.39 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: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR2/FGFR2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 3.2 1.0 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 7.4 1.0 -1.0
dovitinib Hs Inhibitor Inhibition 22.0
SU11652 Hs Inhibitor Inhibition 29.3 14.0 3.0
SB 218078 Hs Inhibitor Inhibition 34.1 83.0 78.0
PKR inhibitor Hs Inhibitor Inhibition 37.6 18.0 3.0
vandetanib Hs Inhibitor Inhibition 38.4
pazopanib Hs Inhibitor Inhibition 40.2
K-252a Hs Inhibitor Inhibition 45.4 20.0 2.0
TWS119 Hs Inhibitor Inhibition 46.1 21.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis
Disease Ontology: DOID:0050462
OMIM: 207410
Orphanet: ORPHA83
Disease:  Apert syndrome
OMIM: 101200
Orphanet: ORPHA87
Disease:  Beare-Stevenson cutis gyrata syndrome
Synonyms: Cutis gyrata - acanthosis nigricans - craniosynostosis [Orphanet: ORPHA1555]
Disease Ontology: DOID:0050660
OMIM: 123790
Orphanet: ORPHA1555
Disease:  Bent bone dysplasia syndrome
Synonyms: FGFR2-related bent bone dysplasia [Orphanet: ORPHA313855]
OMIM: 614592
Orphanet: ORPHA313855
Disease:  Crouzon syndrome
Synonyms: Crouzon disease [Orphanet: ORPHA207]
Disease Ontology: DOID:2339
OMIM: 123500
Orphanet: ORPHA207
Disease:  Jackson-Weiss syndrome
Synonyms: Craniosynostosis - midfacial hypoplasia - foot abnormalities
OMIM: 123150
Orphanet: ORPHA1540
Disease:  Lacrimoauriculodentodigital syndrome
OMIM: 149730
Orphanet: ORPHA2363
Disease:  Pfeiffer syndrome type 1
OMIM: 101600
Orphanet: ORPHA93258
Disease:  Pfeiffer syndrome type 2
OMIM: 101600
Orphanet: ORPHA93259
Disease:  Pfeiffer syndrome type 3
OMIM: 101600
Orphanet: ORPHA93260
Disease:  Saethre-Chotzen syndrome
Disease Ontology: DOID:14768
OMIM: 101400
Orphanet: ORPHA794
Disease:  Scaphocephaly, maxillary retrusion, and mental retardation
Synonyms: Familial scaphocephaly syndrome, McGillivray type [Orphanet: ORPHA168624]
OMIM: 609579
Orphanet: ORPHA168624

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. AstraZeneca. AZD4547. Accessed on 11/09/2014. Modified on 11/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd4547/

3. Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M. (2007) A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol. Cell27 (5): 717-30. [PMID:17803937]

4. 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]

5. 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]

6. Guagnano V, Furet P, Spanka C, Bordas V, Le Douget M, Stamm C, Brueggen J, Jensen MR, Schnell C, Schmid H et al.. (2011) Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J. Med. Chem.54 (20): 7066-83. [PMID:21936542]

7. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J et al.. (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res.68 (12): 4774-82. [PMID:18559524]

8. Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. (1996) Receptor specificity of the fibroblast growth factor family. J. Biol. Chem.271 (25): 15292-7. [PMID:8663044]

9. Pan BS, Chan GK, Chenard M, Chi A, Davis LJ, Deshmukh SV, Gibbs JB, Gil S, Hang G, Hatch H et al.. (2010) MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res.70 (4): 1524-33. [PMID:20145145]

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]

11. Zhao G, Li WY, Chen D, Henry JR, Li HY, Chen Z, Zia-Ebrahimi M, Bloem L, Zhai Y, Huss K et al.. (2011) A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol. Cancer Ther.10 (11): 2200-10. [PMID:21900693]

How to cite this page

Type V RTKs: FGF (fibroblast growth factor) receptor family: fibroblast growth factor receptor 2. Last modified on 02/02/2015. Accessed on 23/05/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1809.