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 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 the catalytic domain of FGFR1 kinase in complex with ARQ 069
PDB Id:  3RHX
Resolution:  2.01Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the tyrosine kinse domain of fibroblast growth factor receptor 1
PDB Id:  1FGK
Resolution:  2.0Å
Species:  Human
References:  14
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)  [15]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
brivanib Hs Inhibition 8.3 pKd 4
pKd 8.3 (Kd 5x10-9 M) [4]
PD166285 Hs Inhibition 7.41 pKi 17
pKi 7.41 (Ki 3.93x10-8 M) [17]
sunitinib Hs Inhibition 6.08 pKi 13
pKi 6.08 (Ki 8.3x10-7 M) [13]
BGJ-398 Hs Inhibition 9.05 pIC50 7
pIC50 9.05 (IC50 9x10-10 M) [7]
LY2874455 Hs Inhibition 8.55 pIC50 25
pIC50 8.55 (IC50 2.8x10-9 M) [25]
AZD4547 Hs Inhibition >8.3 pIC50 2
pIC50 >8.3 (IC50 <5x10-9 M) [2]
compound 8h [PMID 22765894] Hs Inhibition 8.24 pIC50 12
pIC50 8.24 (IC50 5.7x10-9 M) [12]
lucitanib Hs Inhibition 8.15 pIC50 26
pIC50 8.15 (IC50 7x10-9 M) [26]
compound 2c [PMID 24900538] Hs Inhibition 8.06 pIC50 22
pIC50 8.06 (IC50 8.7x10-9 M) [22]
dovitinib Hs Inhibition 7.96 – 8.1 pIC50 19,21
pIC50 7.96 – 8.1 (IC50 1.1x10-8 – 8x10-9 M) [19,21]
CEP-11981 Hs Inhibition 7.89 pIC50 10
pIC50 7.89 (IC50 1.3x10-8 M) [10]
MK-2461 Hs Inhibition 7.19 pIC50 16
pIC50 7.19 (IC50 6.5x10-8 M) [16]
nintedanib Hs Inhibition 7.16 pIC50 9
pIC50 7.16 (IC50 6.9x10-8 M) [9]
pazopanib Hs Inhibition 7.13 pIC50 8
pIC50 7.13 (IC50 7.4x10-8 M) [8]
brivanib Hs Inhibition 6.83 pIC50 3
pIC50 6.83 (IC50 1.48x10-7 M) [3]
SU11652 Hs Inhibition 6.77 pIC50 20
pIC50 6.77 (IC50 1.7x10-7 M) [20]
sorafenib Hs Inhibition 6.24 pIC50 23
pIC50 6.24 (IC50 5.8x10-7 M) [23]
orantinib  Hs Inhibition 5.74 pIC50 11
pIC50 5.74 (IC50 1.81x10-6 M) [11]
SU-14813 Hs Inhibition 5.46 pIC50 18
pIC50 5.46 (IC50 3.5x10-6 M) [18]
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: 4,24

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR1
Ligand Sp. Type Action Affinity Units
tamatinib 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: 1,6

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
TWS119 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
Synonyms: Glioma susceptibility 1; GLM1 [OMIM: 137800]
Disease Ontology: DOID:3074
OMIM: 137800
Orphanet: ORPHA251579
Disease:  Gliosarcoma
Disease Ontology: DOID:3071
Orphanet: ORPHA251576
Disease:  Hartsfield syndrome
OMIM: 615465
Orphanet: ORPHA2117
Disease:  Hypogonadotropic hypogonadism 2 with or without anosmia; HH2
Synonyms: Kallmann syndrome [Orphanet: ORPHA478] [Disease Ontology: DOID:3614]
Normosmic congenital hypogonadotropic hypogonadism [Orphanet: ORPHA432]
Disease Ontology: DOID:3614
OMIM: 147950
Orphanet: ORPHA432, ORPHA478
Disease:  Jackson-Weiss syndrome
Synonyms: Craniosynostosis - midfacial hypoplasia - foot abnormalities
OMIM: 123150
Orphanet: ORPHA1540
Disease:  Myeloid neoplasm associated with FGFR1 rearrangement
Orphanet: ORPHA168953
Disease:  Oligodontia
Orphanet: ORPHA99798
Disease:  Osteoglophonic dysplasia
OMIM: 166250
Orphanet: ORPHA2645
Disease:  Pfeiffer syndrome type 1
OMIM: 101600
Orphanet: ORPHA93258
Disease:  Pilocytic astrocytoma
Disease Ontology: DOID:4851
Orphanet: ORPHA251612
Disease:  Septo-optic dysplasia
OMIM: 182230
Orphanet: ORPHA3157
Disease:  Trigonocephaly 1; TRIGNO1
Synonyms: Isolated trigonocephaly [Orphanet: ORPHA3366]
Metopic craniosynostosis
OMIM: 190440
Orphanet: ORPHA3366

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

3. Bhide RS, Cai ZW, Zhang YZ, Qian L, Wei D, Barbosa S, Lombardo LJ, Borzilleri RM, Zheng X, Wu LI et al.. (2006) Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J. Med. Chem.49 (7): 2143-6. [PMID:16570908]

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. 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]

6. 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]

7. 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]

8. Harris PA, Boloor A, Cheung M, Kumar R, Crosby RM, Davis-Ward RG, Epperly AH, Hinkle KW, Hunter 3rd RN, Johnson JH et al.. (2008) Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J. Med. Chem.51 (15): 4632-40. [PMID:18620382]

9. 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]

10. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J. Med. Chem.55 (2): 903-13. [PMID:22148921]

11. 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]

12. Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR et al.. (2012) The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett.22 (15): 4979-85. [PMID:22765894]

13. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB et al.. (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res.9 (1): 327-37. [PMID:12538485]

14. 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]

15. 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]

16. 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]

17. Panek RL, Lu GH, Klutchko SR, Batley BL, Dahring TK, Hamby JM, Hallak H, Doherty AM, Keiser JA. (1997) In vitro pharmacological characterization of PD 166285, a new nanomolar potent and broadly active protein tyrosine kinase inhibitor. J. Pharmacol. Exp. Ther.283 (3): 1433-44. [PMID:9400019]

18. Patyna S, Laird AD, Mendel DB, O'farrell AM, Liang C, Guan H, Vojkovsky T, Vasile S, Wang X, Chen J et al.. (2006) SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Mol. Cancer Ther.5 (7): 1774-82. [PMID:16891463]

19. 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]

20. 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]

21. Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK. (2005) CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood105 (7): 2941-8. [PMID:15598814]

22. 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 Lett3 (9): 705-9. [PMID:24900538]

23. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M et al.. (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res.64 (19): 7099-109. [PMID:15466206]

24. 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]

25. 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]

26. 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 06/03/2015. Accessed on 28/03/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1808.