fibroblast growth factor receptor 3

Target id: 1810

Nomenclature: fibroblast growth factor receptor 3

Abbreviated Name: FGFR3

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 1 806 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
achondroplasia, thanatophoric dwarfism
HBGFR
sam3
Heparin-binding growth factor receptor
ACH
CD333
CEK2
JTK4
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:  FGFR3 in complex with a Fab
PDB Id:  3GRW
Resolution:  2.1Å
Species:  Human
References:  12
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:  9
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)  [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 9.0 pIC50 7
pIC50 9.0 (IC50 1x10-9 M) [7]
AZD4547 Hs Inhibition >8.3 pIC50 2
pIC50 >8.3 (IC50 <5x10-9 M) [2]
dovitinib Hs Inhibition 8.05 – 8.52 pIC50 13-14
pIC50 8.05 – 8.52 (IC50 9x10-9 – 3x10-9 M) [13-14]
LY2874455 Hs Inhibition 8.19 pIC50 17
pIC50 8.19 (IC50 6.4x10-9 M) [17]
MK-2461 Hs Inhibition 7.3 pIC50 11
pIC50 7.3 (IC50 5x10-8 M) [11]
nintedanib Hs Inhibition 6.97 pIC50 8
pIC50 6.97 (IC50 1.08x10-7 M) [8]
compound 1d [PMID 21493067] Hs Inhibition 6.94 pIC50 15
pIC50 6.94 (IC50 1.15x10-7 M) [15]
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: 4,16

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
tamatinib Hs Inhibitor Inhibition 7.25 pKd
staurosporine Hs Inhibitor Inhibition 7.06 pKd
NVP-TAE684 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
fedratinib 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
tamatinib Hs Inhibitor Inhibition 7.17 pKd
NVP-TAE684 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: 1,5

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:  Achondroplasia
Disease Ontology: DOID:4480
OMIM: 100800
Orphanet: ORPHA15
Disease:  Bladder cancer
Disease Ontology: DOID:11054
OMIM: 109800
Disease:  Camptodactyly, tall stature, and hearing loss syndrome
Synonyms: Camptodactyly - tall stature - scoliosis - hearing loss [Orphanet: ORPHA85164]
OMIM: 610474
Orphanet: ORPHA85164
Disease:  Cervical cancer
Disease Ontology: DOID:4362
OMIM: 603956
Disease:  Crouzon syndrome with acanthosis nigricans
OMIM: 612247
Orphanet: ORPHA93262
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:  Hypochondroplasia
Disease Ontology: DOID:0080041
OMIM: 146000
Orphanet: ORPHA429
Disease:  Isolated brachycephaly
Orphanet: ORPHA35099
Disease:  Isolated cloverleaf skull syndrome
Orphanet: ORPHA2343
Disease:  Isolated plagiocephaly
Orphanet: ORPHA35098
Disease:  Keratosis, seborrheic
Synonyms: Seborrheic keratosis [Disease Ontology: DOID:6498]
Disease Ontology: DOID:6498
OMIM: 182000
Disease:  Lacrimoauriculodentodigital syndrome
OMIM: 149730
Orphanet: ORPHA2363
Disease:  Muenke syndrome
OMIM: 602849
Orphanet: ORPHA53271
Disease:  Myeloma, multiple
Disease Ontology: DOID:9538
OMIM: 254500
References:  3
Disease:  Nevus, epidermal
Disease Ontology: DOID:0050532
OMIM: 162900
Disease:  Saethre-Chotzen syndrome
Disease Ontology: DOID:14768
OMIM: 101400
Orphanet: ORPHA794
Disease:  Severe achondroplasia - developmental delay - acanthosis nigricans
OMIM: 187600
Orphanet: ORPHA85165
Disease:  Testicular germ cell tumor
Synonyms: Seminoma [Disease Ontology: DOID:4440]
Testicular pure germ cell tumor [Disease Ontology: DOID:4087]
Disease Ontology: DOID:4087, DOID:4440
OMIM: 273300
References:  6
Disease:  Thanatophoric dysplasia, type I
Synonyms: Thanatophoric dysplasia [Disease Ontology: DOID:13481]
Disease Ontology: DOID:13481
OMIM: 187600
Orphanet: ORPHA1860
Disease:  Thanatophoric dysplasia, type II
Synonyms: Thanatophoric dysplasia [Disease Ontology: DOID:13481]
Disease Ontology: DOID:13481
OMIM: 187601
Orphanet: ORPHA93274

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. 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]

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. 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. 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]

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. 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]

9. 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]

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. 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]

12. 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]

13. 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]

14. 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]

15. Wang T, Ioannidis S, Almeida L, Block MH, Davies AM, Lamb ML, Scott DA, Su M, Zhang HJ, Alimzhanov M et al.. (2011) In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg. Med. Chem. Lett.21 (10): 2958-61. [PMID:21493067]

16. 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]

17. 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 3. Last modified on 02/03/2015. Accessed on 02/07/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1810.