fibroblast growth factor receptor 3

Nomenclature: fibroblast growth factor receptor 3

Abbreviated Name: FGFR3

Family: Receptor tyrosine kinases

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 1 806 4p16.3 FGFR3 fibroblast growth factor receptor 3
Mouse 1 801 5 B Fgfr3 fibroblast growth factor receptor 3
Rat - 800 14q21 Fgfr3 fibroblast growth factor receptor 3
Previous and Unofficial Names
CD333
ACH
CEK2
JTK4
achondroplasia, thanatophoric dwarfism
HBGFR
Fgfr-3
sam3
Heparin-binding growth factor receptor
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:  FGFR3 in complex with a Fab
PDB Id:  3GRW
Resolution:  2.1Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1
PDB Id:  1RY7
Resolution:  3.2Å
Species:  Human
References:  7
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
FGF-1 (FGF1, P05230), FGF-2 (FGF2, P09038), FGF-9 (FGF9, P31371) > FGF-4 (FGF4, P08620), FGF-8 (FGF8, P55075)  [8]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dovitinib Hs Inhibition 8.52 pIC50 10
pIC50 8.52 (IC50 3x10-9 M) [10]
nintedanib Hs Inhibition 6.97 pIC50 6
pIC50 6.97 (IC50 1.08x10-7 M) [6]
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: 3,11

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR3
Ligand Sp. Type Action Affinity Units
cediranib Hs Inhibitor Inhibition 7.64 pKd
PD-173955 Hs Inhibitor Inhibition 7.32 pKd
R406 Hs Inhibitor Inhibition 7.25 pKd
staurosporine Hs Inhibitor Inhibition 7.06 pKd
TAE 684 Hs Inhibitor Inhibition 7.02 pKd
brivanib Hs Inhibitor Inhibition 6.8 pKd
axitinib Hs Inhibitor Inhibition 6.68 pKd
dovitinib Hs Inhibitor Inhibition 6.64 pKd
sunitinib Hs Inhibitor Inhibition 6.54 pKd
TG-101348 Hs Inhibitor Inhibition 6.44 pKd
Target used in screen: FGFR3(G697C)
Ligand Sp. Type Action Affinity Units
cediranib Hs Inhibitor Inhibition 7.46 pKd
PD-173955 Hs Inhibitor Inhibition 7.34 pKd
R406 Hs Inhibitor Inhibition 7.17 pKd
TAE 684 Hs Inhibitor Inhibition 6.92 pKd
brivanib Hs Inhibitor Inhibition 6.82 pKd
axitinib Hs Inhibitor Inhibition 6.68 pKd
KW-2449 Hs Inhibitor Inhibition 6.55 pKd
staurosporine Hs Inhibitor Inhibition 6.51 pKd
dovitinib Hs Inhibitor Inhibition 6.43 pKd
SU-14813 Hs Inhibitor Inhibition 6.42 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: FGFR3/FGFR3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 3.7 2.0 -0.5
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 5.0 3.0 0.0
SU11652 Hs Inhibitor Inhibition 12.3 8.0 1.0
dovitinib Hs Inhibitor Inhibition 12.4
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 26.7 125.0 132.0
Syk inhibitor Hs Inhibitor Inhibition 33.8 17.0 14.0
PKR inhibitor Hs Inhibitor Inhibition 34.8 19.0 9.0
SB 218078 Hs Inhibitor Inhibition 36.3 82.0 92.0
pazopanib Hs Inhibitor Inhibition 39.3
sunitinib Hs Inhibitor Inhibition 39.7
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Isolated brachycephaly
Orphanet:  35099
References: 
Mutations not determined
Disease:  Achondroplasia
OMIM:  100800
Orphanet:  15
References: 
Mutations not determined
Disease:  Hypochondroplasia
OMIM:  146000
Orphanet:  429
References: 
Mutations not determined
Disease:  Muenke syndrome
OMIM:  602849
Orphanet:  53271
References: 
Mutations not determined
Disease:  Saethre-Chotzen syndrome
OMIM:  101400
Orphanet:  794
References: 
Mutations not determined
Disease:  Crouzon syndrome with acanthosis nigricans
OMIM:  612247
Orphanet:  93262
References: 
Mutations not determined
Disease:  Camptodactyly, tall stature, and hearing loss syndrome
OMIM:  610474
Orphanet:  85164
References: 
Mutations not determined
Disease:  Lacrimoauriculodentodigital syndrome
OMIM:  149730
Orphanet:  2363
References: 
Mutations not determined
Disease:  Thanatophoric dysplasia, type II
OMIM:  187601
Orphanet:  93274
References: 
Mutations not determined
Disease:  Isolated plagiocephaly
Orphanet:  35098
References: 
Mutations not determined
Disease:  Isolated cloverleaf skull syndrome
Orphanet:  2343
References: 
Mutations not determined
Disease:  Giant cell glioblastoma
Orphanet:  251579
References: 
Mutations not determined
Disease:  Beare-Stevenson cutis gyrata syndrome
Orphanet:  1555
References: 
Mutations not determined
Disease:  Thanatophoric dysplasia, type I
OMIM:  187600
Orphanet:  1860, 85165
References: 
Mutations not determined
Disease:  Gliosarcoma
Orphanet:  251576
References: 
Mutations not determined
Disease:  Cervical cancer, somatic
OMIM:  603956
References: 
Mutations not determined
Disease:  Testicular germ cell tumor
OMIM:  273300
References:  5
Mutations not determined
Disease:  Myeloma, multiple
OMIM:  254500
References:  2
Mutations not determined
Disease:  Keratosis, seborrheic
OMIM:  182000
References: 
Mutations not determined
Disease:  Nevus, epidermal, somatic
OMIM:  162900
References: 
Mutations not determined
Disease:  Bladder cancer, somatic
OMIM:  109800
References: 
Mutations not determined

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. Chesi M, Nardini E, Brents LA, Schröck E, Ried T, Kuehl WM, Bergsagel PL. (1997) Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat. Genet.16 (3): 260-4. [PMID:9207791]

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. 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]

5. Goriely A, Hansen RM, Taylor IB, Olesen IA, Jacobsen GK, McGowan SJ, Pfeifer SP, McVean GA, Rajpert-De Meyts E, Wilkie AO. (2009) Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. Nat. Genet.41 (11): 1247-52. [PMID:19855393]

6. 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]

7. Olsen SK, Ibrahimi OA, Raucci A, Zhang F, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M. (2004) Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity. Proc. Natl. Acad. Sci. U.S.A.101 (4): 935-40. [PMID:14732692]

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. Qing J, Du X, Chen Y, Chan P, Li H, Wu P, Marsters S, Stawicki S, Tien J, Totpal K et al.. (2009) Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice. J. Clin. Invest.119 (5): 1216-29. [PMID:19381019]

10. 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]

11. 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]

How to cite this page

Receptor tyrosine kinases: fibroblast growth factor receptor 3. Last modified on 13/05/2014. Accessed on 25/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1810.