Top ▲

fibroblast growth factor receptor 2

Click here for help

Target id: 1809

Nomenclature: fibroblast growth factor receptor 2

Abbreviated Name: FGFR2

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 1 821 10q26.13 FGFR2 fibroblast growth factor receptor 2
Mouse 1 821 7 F3 Fgfr2 fibroblast growth factor receptor 2
Rat - 841 1q37 Fgfr2 fibroblast growth factor receptor 2
Previous and Unofficial Names Click here for help
Pfeiffer syndrome | bacteria-expressed kinase | craniofacial dysostosis 1 | Crouzon syndrome | Jackson-Weiss syndrome | keratinocyte growth factor receptor | Fgfr7 | BEK | CD332 | CEK3 | CFD1 | ECT1 | JWS | KGFR | TK14 | TK25
Database Links Click here for help
Alphafold P21802 (Hs), P21803 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL4142 (Hs), CHEMBL3648 (Mm)
DrugBank Target P21802 (Hs)
Ensembl Gene ENSG00000066468 (Hs), ENSMUSG00000030849 (Mm), ENSRNOG00000016374 (Rn)
Entrez Gene 2263 (Hs), 14183 (Mm), 25022 (Rn)
Human Protein Atlas ENSG00000066468 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2263 (Hs), mmu:14183 (Mm), rno:25022 (Rn)
OMIM 176943 (Hs)
Orphanet ORPHA132262 (Hs)
Pharos P21802 (Hs)
RefSeq Nucleotide NM_000141 (Hs), NM_010207 (Mm), NM_012712 (Rn)
RefSeq Protein NP_000132 (Hs), NP_963895 (Mm), NP_034337 (Mm), NP_036844 (Rn)
UniProtKB P21802 (Hs), P21803 (Mm)
Wikipedia FGFR2 (Hs)
Selected 3D Structures Click here for help
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:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure Analysis of the FGF10-FGFR2b Complex
PDB Id:  1NUN
Ligand:  FGF-10
Resolution:  2.9Å
Species:  Human
References:  26
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Endogenous ligand (Human)
FGF-10 (FGF10, O15520)  [26]
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)  [15]

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
compound 29 [PMID: 36356320] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 20
⤷ pIC50 9.0 (IC50 1x10-9 M) [20]
futibatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 18
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [18]
PRN1371 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 3
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [3]
segigratinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pIC50 17
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [17]
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 8.9 pIC50 8
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [8]
derazantinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 10
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [10]
erdafitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 19
⤷ pIC50 8.6 (IC50 2.29x10-9 M) [19]
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 27
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [27]
tasurgratinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 6
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [6]
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 pIC50 2
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [2]
compound 7 [Nguyen et al., 2023] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 14
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [14]
zoligratinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 13
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [13]
nintedanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 11
⤷ pIC50 7.4 (IC50 3.7x10-8 M) [11]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 16
⤷ pIC50 7.4 (IC50 3.9x10-8 M) [16]
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 24
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [24]
lirafugratinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition >7.0 pIC50 21
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [21]
Description: Determiend in a FGFR2 biochemical caliper assay
resigratinib Small molecule or natural product Hs Inhibition >7.0 pIC50 12
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [12]
BLU-9931 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 9
⤷ pIC50 6.3 (IC50 4.93x10-7 M) [9]
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
palifermin Peptide Approved drug Primary target of this compound Hs Agonist - -
⤷
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
alofanib Small molecule or natural product Hs Inhibition >8.0 pIC50 22
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [22]
Description: Inhibition of FGF2-induced phoshphorylation of FRS2α in KATO III cells.
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
bemarituzumab Peptide Click here for species-specific activity table Hs Binding 9.2 pKd 25
⤷ pKd 9.2 (Kd 5.8x10-10 M) [25]
Description: Binding affinity to FGFR2a ECD by SPR.
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: 5,23
Key to terms and symbols Click column headers to sort
Target used in screen: FGFR2
Ligand Sp. Type Action Value Parameter
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 7.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
brivanib Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
dovitinib 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: 1,7
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.2 1.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 1.0 -1.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 22.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 29.3 14.0 3.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 34.1 83.0 78.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 37.6 18.0 3.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 38.4
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 40.2
K-252a Small molecule or natural product Hs Inhibitor Inhibition 45.4 20.0 2.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 46.1 21.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune system development
Clinically-Relevant Mutations and Pathophysiology Click here for help
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
Synonyms: LADD syndrome [Disease Ontology: DOID:0050331]
Disease Ontology: DOID:0050331
OMIM: 149730
Orphanet: ORPHA2363
Disease:  Pfeiffer syndrome type 1
Synonyms: Pfeiffer syndrome [Disease Ontology: DOID:14705]
Disease Ontology: DOID:14705
OMIM: 101600
Orphanet: ORPHA93258
Disease:  Pfeiffer syndrome type 2
Synonyms: Pfeiffer syndrome [Disease Ontology: DOID:14705]
Disease Ontology: DOID:14705
OMIM: 101600
Orphanet: ORPHA93259
Disease:  Pfeiffer syndrome type 3
Synonyms: Pfeiffer syndrome [Disease Ontology: DOID:14705]
Disease Ontology: DOID:14705
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

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. Brameld KA, Owens TD, Verner E, Venetsanakos E, Bradshaw JM, Phan VT, Tam D, Leung K, Shu J, LaStant J et al.. (2017) Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors. J Med Chem, 60 (15): 6516-6527. [PMID:28665128]

4. 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 Cell, 27 (5): 717-30. [PMID:17803937]

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. 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.

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. 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]

9. 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]

10. 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]

11. 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]

12. Kaldor SW, Tyhonas J, Murphy EA, Kanouni T, Arnold LD, Kania R, Cox JM. (2021) Inhibitors of fibroblast growth factor receptor kinases. Patent number: WO2021247969A1. Assignee: Kinnate Biopharma Inc.. Priority date: 04/06/2021. Publication date: 09/12/2021.

13. Nakanishi Y, Akiyama N, Tsukaguchi T, Fujii T, Sakata K, Sase H, Isobe T, Morikami K, Shindoh H, Mio T et al.. (2014) The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther, 13 (11): 2547-58. [PMID:25169980]

14. Nguyen MH, Ye HF, Xu Y, Truong L, Horsey A, Styduhar ED, Frascella M, Leffet L, Federowicz K, Behshad E et al.. (2023) Discovery of Orally Bioavailable FGFR2/FGFR3 Dual Inhibitors via Structure-Guided Scaffold Repurposing Approach. ACS Medicinal Chemistry Letters, 14 (3): 312–318. DOI: 10.1021/acsmedchemlett.3c00003

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. Peng X, Hou P, Chen Y, Dai Y, Ji Y, Shen Y, Su Y, Liu B, Wang Y, Sun D et al.. (2019) Preclinical evaluation of 3D185, a novel potent inhibitor of FGFR1/2/3 and CSF-1R, in FGFR-dependent and macrophage-dominant cancer models. J Exp Clin Cancer Res, 38 (1): 372. [PMID:31438996]

18. Sagara T, Ito S, Otsuki S, Sootome H. (2013) 3,5-disubstituted alkynylbenzene compound and salt thereof. Patent number: WO2013108809. Assignee: Taiho Pharmaceutical Co., Ltd.. Priority date: 19/01/2012. Publication date: 25/07/2013.

19. Saxty G, Murray CW, Berdini V, Besong GE, Hamlett CCF, Johnson CN, Woodhead SJ, Reader M, Rees DC, Mevellec LA et al.. (2011) Pyrazolyl quinazoline kinase inhibitors. Patent number: WO2011135376 A1. Assignee: Astex Therapeutics Limited. Priority date: 30/04/2010. Publication date: 03/11/2011.

20. Shvartsbart A, Roach JJ, Witten MR, Koblish H, Harris JJ, Covington M, Hess R, Lin L, Frascella M, Truong L et al.. (2022) Discovery of Potent and Selective Inhibitors of Wild-Type and Gatekeeper Mutant Fibroblast Growth Factor Receptor (FGFR) 2/3. J Med Chem, 65 (22): 15433-15442. [PMID:36356320]

21. Toure B, Schoenherr H, Taylor AM, Giordanetto F, Moustakas DT, McLean TH, Hudson BM, Mader MM, Ayaz P, Sharon DA et al.. (2020) Fgfr inhibitors and methods of use thereof. Patent number: WO2020231990A1. Assignee: Relay Therapeutics, Inc., D.E. Shaw Research, Llc. Priority date: 12/05/2020. Publication date: 19/11/2020.

22. Tsimafeyeu I, Ludes-Meyers J, Stepanova E, Daeyaert F, Khochenkov D, Joose JB, Solomko E, Van Akene K, Peretolchina N, Yin W et al.. (2016) Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models. Eur J Cancer, 61: 20-8. [PMID:27136102]

23. 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]

24. Wu L, Zhang C, He C, Sun Y, Lu L, Qian D-Q, Xu M, Zhou J, Yao W. (2014) Substituted tricyclic compounds as FGFR inhibitors. Patent number: WO2014007951. Assignee: Incyte Corporation. Priority date: 13/06/2012. Publication date: 09/01/2014.

25. Xiang H, Liu L, Gao Y, Ahene A, Macal M, Hsu AW, Dreiling L, Collins H. (2020) Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. Cancer Chemother Pharmacol, 86 (5): 595-606. [PMID:32965540]

26. Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M. (2003) Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Natl Acad Sci USA, 100 (5): 2266-71. [PMID:12591959]

27. 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 06/03/2024. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1809.