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fibroblast growth factor receptor 1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1808

Nomenclature: fibroblast growth factor receptor 1

Abbreviated Name: FGFR1

Family: Type V RTKs: FGF (fibroblast growth factor) receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 822 8p11.23 FGFR1 fibroblast growth factor receptor 1
Mouse 1 822 8 14.12 cM Fgfr1 fibroblast growth factor receptor 1
Rat 1 822 16q12.4 Fgfr1 Fibroblast growth factor receptor 1
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P11362 (Hs), P16092 (Mm), Q04589 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL3650 (Hs), CHEMBL3960 (Mm), CHEMBL4523276 (Rn)
DrugBank Target P11362 (Hs)
Ensembl Gene ENSG00000077782 (Hs), ENSMUSG00000031565 (Mm), ENSRNOG00000016050 (Rn)
Entrez Gene 2260 (Hs), 14182 (Mm), 79114 (Rn)
Human Protein Atlas ENSG00000077782 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2260 (Hs), mmu:14182 (Mm), rno:79114 (Rn)
OMIM 136350 (Hs)
Orphanet ORPHA121802 (Hs)
Pharos P11362 (Hs)
RefSeq Nucleotide NM_001174063 (Hs), NM_010206 (Mm), NM_024146 (Rn)
RefSeq Protein NP_056934 (Hs), NP_034336 (Mm), NP_001073377 (Mm), NP_001073378 (Mm), NP_077060 (Rn)
SynPHARM 80719 (in complex with BGJ-398)
UniProtKB P11362 (Hs), P16092 (Mm), Q04589 (Rn)
Wikipedia FGFR1 (Hs)
Selected 3D Structures Click here for help
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:  9
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:  23
Image of receptor 3D structure from RCSB PDB
Description:  FGFR1 in complex with AZD4547.
PDB Id:  4V05
Ligand:  fexagratinib
Resolution:  2.57Å
Species:  Human
References:  39
Image of receptor 3D structure from RCSB PDB
Description:  Human FGFR1 kinase in complex with CH5183284 (DEBIO1347).
PDB Id:  5B7V
Ligand:  zoligratinib
Resolution:  2.15Å
Species:  Human
References:  24
Enzyme Reaction Click here for help
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)  [26]

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
brivanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pKd 8
⤷ pKd 8.3 (Kd 5x10-9 M) [8]
rogaratinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pKi 6
⤷ pKi 7.9 (Ki 1.22x10-8 M) [6]
Description: At a high ATP level.
PD166285 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 28
⤷ pKi 7.4 (Ki 3.93x10-8 M) [28]
toceranib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pKi 20
⤷ pKi 6.3 (Ki 5x10-7 M) [20]
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pKi 22
⤷ pKi 6.1 (Ki 8.3x10-7 M) [22]
segigratinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.3 pIC50 30
⤷ pIC50 9.3 (IC50 5x10-10 M) [30]
infigratinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 12
⤷ pIC50 9.1 (IC50 9x10-10 M) [12]
PRN1371 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 – 9.2 pIC50 5
⤷ pIC50 9.2 (IC50 6x10-10 M) [5]
Description: In a kinase selectivity profiling assay.
pIC50 8.8 (IC50 1.5x10-9 M) [5]
erdafitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 33
⤷ pIC50 8.9 (IC50 1.14x10-9 M) [33]
fexagratinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >8.3 – 9.1 pIC50 2,21
⤷ pIC50 >8.3 – 9.1 (IC50 <5x10-9 – 7x10-10 M) [2,21]
tinengotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 43
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [43]
LY2874455 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 46
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [46]
compound 7r [PMID: 26080733] Small molecule or natural product Hs Inhibition 8.5 pIC50 21
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [21]
futibatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 32
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [32]
derazantinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 14
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [14]
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 – 8.4 pIC50 19,45
⤷ pIC50 8.4 (IC50 4x10-9 M) [19]
pIC50 8.2 (IC50 6.2x10-9 M) [45]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 19
⤷ pIC50 8.2 (IC50 5.7x10-9 M) [19]
tasurgratinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 10
⤷ pIC50 8.2 (IC50 5.8x10-9 M) [10]
lucitanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 47
⤷ pIC50 8.1 (IC50 7x10-9 M) [47]
compound 2c [PMID: 24900538] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 40
⤷ pIC50 8.1 (IC50 8.7x10-9 M) [40]
zoligratinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 24
⤷ pIC50 8.0 (IC50 9.2x10-9 M) [24]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 – 8.1 pIC50 31,38
⤷ pIC50 8.0 – 8.1 (IC50 1.1x10-8 – 8x10-9 M) [31,38]
CEP-11981 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 17
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [17]
catequentinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 2x10-8 M) [7]
Description: in vitro activity
compound 29 [PMID: 36356320] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 34
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [34]
pexmetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 3
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [3]
SU5402 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 37
⤷ pIC50 7.5 (IC50 3x10-8 M) [37]
surufatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 35
⤷ pIC50 7.3 (IC50 5.3x10-8 M) [35]
Description: Using a Transcreener FP technology assay.
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 27
⤷ pIC50 7.2 (IC50 6.5x10-8 M) [27]
nintedanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 16
⤷ pIC50 7.2 (IC50 6.9x10-8 M) [16]
pazopanib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.1 pIC50 15
⤷ pIC50 7.1 (IC50 7.4x10-8 M) [15]
compound 7 [Nguyen et al., 2023] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 25
⤷ pIC50 7.1 (IC50 8.9x10-8 M) [25]
pemigatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >7.0 pIC50 44
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [44]
brivanib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 4
⤷ pIC50 6.8 (IC50 1.48x10-7 M) [4]
SU11652 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 36
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [36]
sorafenib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 41,45
⤷ pIC50 6.2 (IC50 5.8x10-7 M) [45]
pIC50 6.2 (IC50 5.8x10-7 M) [41]
BLU-9931 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 13
⤷ pIC50 6.2 (IC50 5.91x10-7 M) [13]
orantinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pIC50 18
⤷ pIC50 5.7 (IC50 1.81x10-6 M) [18]
SU-14813 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 29
⤷ pIC50 5.5 (IC50 3.5x10-6 M) [29]
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: 8,42
Key to terms and symbols Click column headers to sort
Target used in screen: FGFR1
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
brivanib Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.4 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: 1,11
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.7 0.5 -0.5
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 1.0 -1.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 18.2
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.3 7.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 24.2 113.0 81.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 27.9 2.0 -1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 29.1 72.0 41.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 36.1 5.0 -4.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 38.2 10.0 0.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 39.3 2.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
A FGFR1 isoform (FGFR1(IIIc)) in complex with the Klotho protein (KL; Q9UEF7) forms a high affinity receptor for FGF-23.
In the choroid plexus (the interface between the brain and immune system) Klotho enhances FGF23 signalling and activation of the NLRP3 inflammasome in resident macrophages, in a system that regulates the level of immune system activation at the blood-brain barrier. Experimental evidence from mice suggests that age-related decline of Klotho in the choroid plexus may be part of the mechanism responisble for "inflammaging", the progressive systemic increase in brain inflammation that is believed to contribute to neurodegeneration in old age [48].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
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
Synonyms: Osteoglophonic dwarfism [Orphanet: ORPHA2645]
OMIM: 166250
Orphanet: ORPHA2645
Disease:  Pfeiffer syndrome type 1
Synonyms: Pfeiffer syndrome [Disease Ontology: DOID:14705]
Disease Ontology: DOID:14705
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

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

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7. Chen GP. (2008) Spiro substituted compounds as angiogenesis inhibitors. Patent number: WO2008112407 A1. Assignee: Advenchen Laboratories, Llc. Priority date: 14/03/2007. Publication date: 18/09/2008.

8. 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]

9. 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]

10. Funasaka S, Okada S, Tanaka K, Nagao S, Ohashi I, Yamane Y, Nakatani Y,Karouji Y. (2014) Monocyclic pyridine derivative. Patent number: WO2014129477A1. Assignee: Eisai R & D. Priority date: 20/02/2013. Publication date: 28/08/2014.

11. 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]

12. 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]

13. Hagel M, Miduturu C, Sheets M, Rubin N, Weng W, Stransky N, Bifulco N, Kim JL, Hodous B, Brooijmans N et al.. (2015) First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov, 5 (4): 424-37. [PMID:25776529]

14. Hall TG, Yu Y, Eathiraj S, Wang Y, Savage RE, Lapierre JM, Schwartz B, Abbadessa G. (2016) Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS ONE, 11 (9): e0162594. [PMID:27627808]

15. 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]

16. 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]

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21. Liu J, Peng X, Dai Y, Zhang W, Ren S, Ai J, Geng M, Li Y. (2015) Design, synthesis and biological evaluation of novel FGFR inhibitors bearing an indazole scaffold. Org Biomol Chem, 13 (28): 7643-54. [PMID:26080733]

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How to cite this page

Type V RTKs: FGF (fibroblast growth factor) receptor family: fibroblast growth factor receptor 1. Last modified on 12/06/2024. Accessed on 10/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1808.