fibroblast growth factor receptor 1

Target id: 1808

Nomenclature: fibroblast growth factor receptor 1

Abbreviated Name: FGFR1

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 1 820 8p12 FGFR1 fibroblast growth factor receptor 1
Mouse 1 822 8 Fgfr1 fibroblast growth factor receptor 1
Rat 1 822 16q12.4 Fgfr1 Fibroblast growth factor receptor 1
Previous and Unofficial Names
BFGFR
CD331
CEK
FLT2
fms-related tyrosine kinase 2
Pfeiffer syndrome
basic fibroblast growth factor receptor 1
FGF receptor-1
MFR
Eask
Hspy
KAL2
FLG
N-SAM
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
Orphanet Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1
PDB Id:  1FGK
Resolution:  2.0Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the catalytic domain of FGFR1 kinase in complex with ARQ 069
PDB Id:  3RHX
Resolution:  2.01Å
Species:  Human
References:  4
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
FGF-1 (FGF1, P05230), FGF-2 (FGF2, P09038), FGF-4 (FGF4, P08620) > FGF-5 (FGF5, P12034), FGF-6 (FGF6, P10767)  [10]
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 9.05 pIC50 6
pIC50 9.05 (IC50 9x10-10 M) [6]
AZD4547 Hs Inhibition >8.3 pIC50 2
pIC50 >8.3 (IC50 <5x10-9 M) [2]
lucitanib Hs Inhibition 8.15 pIC50 14
pIC50 8.15 (IC50 7x10-9 M) [14]
dovitinib Hs Inhibition 7.96 pIC50 11
pIC50 7.96 (IC50 1.1x10-8 M) [11]
nintedanib Hs Inhibition 7.16 pIC50 7
pIC50 7.16 (IC50 6.9x10-8 M) [7]
SU11652 Hs Inhibition 6.77 pIC50 12
pIC50 6.77 (IC50 1.7x10-7 M) [12]
orantinib  Hs Inhibition 5.74 pIC50 8
pIC50 5.74 (IC50 1.81x10-6 M) [8]
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: 3,13

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR1
Ligand Sp. Type Action Affinity Units
R406 Hs Inhibitor Inhibition 7.36 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.33 pKd
cediranib Hs Inhibitor Inhibition 7.28 pKd
PD-173955 Hs Inhibitor Inhibition 7.21 pKd
staurosporine Hs Inhibitor Inhibition 7.05 pKd
brivanib Hs Inhibitor Inhibition 7.0 pKd
dovitinib Hs Inhibitor Inhibition 6.82 pKd
fedratinib Hs Inhibitor Inhibition 6.55 pKd
lestaurtinib Hs Inhibitor Inhibition 6.51 pKd
KW-2449 Hs Inhibitor Inhibition 6.43 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: FGFR1/FGFR1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.7 0.5 -0.5
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 6.6 1.0 -1.0
dovitinib Hs Inhibitor Inhibition 18.2
SU11652 Hs Inhibitor Inhibition 20.3 7.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 24.2 113.0 81.0
indirubin derivative E804 Hs Inhibitor Inhibition 27.9 2.0 -1.0
SB 218078 Hs Inhibitor Inhibition 29.1 72.0 41.0
midostaurin Hs Inhibitor Inhibition 36.1 5.0 -4.0
aurora kinase/Cdk inhibitor Hs Inhibitor Inhibition 38.2 10.0 0.0
GSK-3beta inhibitor XII Hs Inhibitor Inhibition 39.3 2.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Giant cell glioblastoma
Orphanet:  251579
Disease:  Gliosarcoma
Orphanet:  251576
Disease:  Hartsfield syndrome
OMIM:  615465
Orphanet:  2117
Disease:  Hypogonadotropic hypogonadism 2 with or without anosmia
OMIM:  147950
Orphanet:  432
Disease:  Kallmann syndrome
Orphanet:  478
Disease:  Myeloid neoplasm associated with FGFR1 rearrangement
Orphanet:  168953
Disease:  Oligodontia
Orphanet:  99798
Disease:  Osteoglophonic dysplasia
OMIM:  166250
Orphanet:  2645
Disease:  Pfeiffer syndrome type 1
OMIM:  101600
Orphanet:  93258
Disease:  Pilocytic astrocytoma
Orphanet:  251612
Disease:  Septo-optic dysplasia
Orphanet:  3157
Disease:  Trigonocephaly 1
OMIM:  190440
Orphanet:  3366

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. 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]

4. Eathiraj S, Palma R, Hirschi M, Volckova E, Nakuci E, Castro J, Chen CR, Chan TC, France DS, Ashwell MA. (2011) A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J. Biol. Chem.286 (23): 20677-87. [PMID:21454610]

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. Kammasud N, Boonyarat C, Sanphanya K, Utsintong M, Tsunoda S, Sakurai H, Saiki I, André I, Grierson DS, Vajragupta O. (2009) 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. Bioorg. Med. Chem. Lett.19 (3): 745-50. [PMID:19110422]

9. Mohammadi M, Schlessinger J, Hubbard SR. (1996) Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism. Cell86 (4): 577-87. [PMID:8752212]

10. 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]

11. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M et al.. (2009) Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J. Med. Chem.52 (2): 278-92. [PMID:19113866]

12. Sun L, Liang C, Shirazian S, Zhou Y, Miller T, Cui J, Fukuda JY, Chu JY, Nematalla A, Wang X et al.. (2003) Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem.46 (7): 1116-9. [PMID:12646019]

13. 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]

14. Zhou Y, Chen Y, Tong L, Xie H, Wen W, Zhang J, Xi Y, Shen Y, Geng M, Wang Y et al.. (2012) AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR. J. Cell. Mol. Med.16 (10): 2321-30. [PMID:22304225]

How to cite this page

Type V RTKs: FGF (fibroblast growth factor) receptor family: fibroblast growth factor receptor 1. Last modified on 04/11/2014. Accessed on 24/11/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1808.