platelet-derived growth factor receptor, beta polypeptide

Target id: 1804

Nomenclature: platelet-derived growth factor receptor, beta polypeptide

Abbreviated Name: PDGFRβ

Family: Type III RTKs: PDGFR, CSFR, Kit, FLT3 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 1106 5q33.1 PDGFRB platelet-derived growth factor receptor, beta polypeptide
Mouse 1 1099 18 Pdgfrb platelet derived growth factor receptor, beta polypeptide
Rat 1 1097 18q12.1 Pdgfrb platelet derived growth factor receptor, beta polypeptide
Previous and Unofficial Names
CD140b
JTK12
PDGFR1
PDGFR-beta
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:  The structure of a platelet derived growth factor receptor complex
PDB Id:  3MJG
Resolution:  2.3Å
Species:  Human
References:  19
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
PDGF
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
crenolanib Hs Inhibition 8.49 pKd 9
pKd 8.49 (Kd 3.2x10-9 M) [9]
SU11652 Hs Inhibition 8.52 pIC50 20
pIC50 8.52 (IC50 3x10-9 M) [20]
PDGF receptor tyrosine kinase inhibitor IV Hs Inhibition 8.38 pIC50 11
pIC50 8.38 (IC50 4.2x10-9 M) [11]
cediranib Hs Inhibition 8.3 pIC50 21
pIC50 8.3 (IC50 5x10-9 M) [21]
dovitinib Hs Inhibition 8.3 pIC50 18
pIC50 8.3 (IC50 5x10-9 M) [18]
sunitinib Hs Inhibition 8.2 pIC50 13
pIC50 8.2 (IC50 5.7x10-9 M) [13]
lucitanib Hs Inhibition 8.1 pIC50 23
pIC50 8.1 (IC50 8x10-9 M) [23]
PDGF RTK inhibitor Hs Inhibition 7.92 pIC50 6
pIC50 7.92 (IC50 1.2x10-8 M) [6]
Description: Inhibition of PDGFR autophosphorylation in human G292 cells
orantinib  Hs Inhibition 7.3 pIC50 12
pIC50 7.3 (IC50 5x10-8 M) [12]
nintedanib Hs Inhibition 7.19 pIC50 10
pIC50 7.19 (IC50 6.5x10-8 M) [10]
linifanib Hs Inhibition 7.18 pIC50 1
pIC50 7.18 (IC50 6.6x10-8 M) [1]
PDGF receptor tyrosine kinase inhibitor III Hs Inhibition 7.1 pIC50 15
pIC50 7.1 (IC50 8x10-8 M) [15]
AGL 2043 Hs Inhibition 7.05 pIC50 8
pIC50 7.05 (IC50 9x10-8 M) [8]
Description: Using purified human PDGFRβ
Flt-3 inhibitor II Hs Inhibition 6.77 pIC50 14
pIC50 6.77 (IC50 1.71x10-7 M) [14]
vatalanib Hs Inhibition 6.22 pIC50 3
pIC50 6.22 (IC50 6x10-7 M) [3]
masitinib Hs Inhibition 6.1 pIC50 5
pIC50 6.1 (IC50 8x10-7 M) [5]
GTP-14564 Hs Inhibition 6.0 pIC50 16
pIC50 6.0 (IC50 1x10-6 M) [16]
Inhibitor Comments
Note that sunitinib inhibits a range of additional kinases, including platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3) and colony stimulating factor receptor Type 1 (CSF-1R).
The experiments measuring the ability of PDGF RTK inhibitor to inhibit PDGFR autophosphorylation were carried out in intact human cells, so it is impossible to specify the isozyme involved in the interaction. We nominally map the interaction to the beta isozyme for data retrieval purposes only.
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: 4,22

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRB
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 10.12 pKd
SU-14813 Hs Inhibitor Inhibition 9.54 pKd
Ki-20227 Hs Inhibitor Inhibition 9.54 pKd
cediranib Hs Inhibitor Inhibition 9.49 pKd
axitinib Hs Inhibitor Inhibition 9.24 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
foretinib Hs Inhibitor Inhibition 9.02 pKd
PD-173955 Hs Inhibitor Inhibition 8.85 pKd
staurosporine Hs Inhibitor Inhibition 8.74 pKd
linifanib Hs Inhibitor Inhibition 8.72 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: 2,7

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRβ/PDGFRb
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 2.3 3.0 1.0
dasatinib Hs Inhibitor Inhibition 2.5
SU11652 Hs Inhibitor Inhibition 9.3 1.0 1.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 11.4 120.0 111.0
sorafenib Hs Inhibitor Inhibition 12.0
K-252a Hs Inhibitor Inhibition 14.6 46.0 8.0
midostaurin Hs Inhibitor Inhibition 14.8 46.0 25.0
dovitinib Hs Inhibitor Inhibition 17.2
masitinib Hs Inhibitor Inhibition 17.3
sunitinib Hs Inhibitor Inhibition 17.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Basal ganglia calcification, idiopathic, 4
OMIM:  615007
Disease:  Bilateral striopallidodentate calcinosis
Orphanet:  1980
References:  17
Disease:  Chronic myelomonocytic leukemia
Orphanet:  98823
Disease:  Idiopathic hypereosinophilic syndrome
Orphanet:  3260
Disease:  Myeloid neoplasm associated with PDGFRB rearrangement
Orphanet:  168950
Disease:  Myeloproliferative disorder with eosinophilia
OMIM:  131440
Disease:  Myofibromatosis, infantile, 1
OMIM:  228550
Orphanet:  2591
Disease:  Unclassified chronic myeloproliferative disease
Orphanet:  86830

References

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1. Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS et al.. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer Ther.5 (4): 995-1006. [PMID:16648571]

2. 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]

3. Bold G, Altmann KH, Frei J, Lang M, Manley PW, Traxler P, Wietfeld B, Brüggen J, Buchdunger E, Cozens R et al.. (2000) New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J. Med. Chem.43 (12): 2310-23. [PMID:10882357]

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. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W et al.. (2009) Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE4 (9): e7258. [PMID:19789626]

6. Furuta T, Sakai T, Senga T, Osawa T, Kubo K, Shimizu T, Suzuki R, Yoshino T, Endo M, Miwa A. (2006) Identification of potent and selective inhibitors of PDGF receptor autophosphorylation. J. Med. Chem.49 (7): 2186-92. [PMID:16570914]

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. Gazit A, Yee K, Uecker A, Böhmer FD, Sjöblom T, Ostman A, Waltenberger J, Golomb G, Banai S, Heinrich MC et al.. (2003) Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase, Flt3 and Kit. Bioorg. Med. Chem.11 (9): 2007-18. [PMID:12670652]

9. Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. (2012) Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin. Cancer Res.18 (16): 4375-84. [PMID:22745105]

10. 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]

11. Ho CY, Ludovici DW, Maharoof US, Mei J, Sechler JL, Tuman RW, Strobel ED, Andraka L, Yen HK, Leo G et al.. (2005) (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. J. Med. Chem.48 (26): 8163-73. [PMID:16366598]

12. 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]

13. Kitagawa D, Yokota K, Gouda M, Narumi Y, Ohmoto H, Nishiwaki E, Akita K, Kirii Y. (2013) Activity-based kinase profiling of approved tyrosine kinase inhibitors. Genes Cells18 (2): 110-22. [PMID:23279183]

14. Mahboobi S, Uecker A, Sellmer A, Cénac C, Höcher H, Pongratz H, Eichhorn E, Hufsky H, Trümpler A, Sicker M et al.. (2006) Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem.49 (11): 3101-15. [PMID:16722630]

15. Matsuno K, Ushiki J, Seishi T, Ichimura M, Giese NA, Yu JC, Takahashi S, Oda S, Nomoto Y. (2003) Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 3. Replacement of quinazoline moiety and improvement of metabolic polymorphism of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives. J. Med. Chem.46 (23): 4910-25. [PMID:14584942]

16. Murata K, Kumagai H, Kawashima T, Tamitsu K, Irie M, Nakajima H, Suzu S, Shibuya M, Kamihira S, Nosaka T et al.. (2003) Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3). J. Biol. Chem.278 (35): 32892-8. [PMID:12815052]

17. Nicolas G, Pottier C, Charbonnier C, Guyant-Maréchal L, Le Ber I, Pariente J, Labauge P, Ayrignac X, Defebvre L, Maltête D et al.. (2013) Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification. Brain136 (Pt 11): 3395-407. [PMID:24065723]

18. 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]

19. Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X. (2010) Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Proc. Natl. Acad. Sci. U.S.A.107 (25): 11307-12. [PMID:20534510]

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. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO et al.. (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res.65 (10): 4389-400. [PMID:15899831]

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23. 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 III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: platelet-derived growth factor receptor, beta polypeptide. Last modified on 05/11/2014. Accessed on 29/11/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1804.