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
DrugBank Target
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:  The structure of a platelet derived growth factor receptor complex
PDB Id:  3MJG
Resolution:  2.3Å
Species:  Human
References:  31
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
PDGF

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
AC710 Hs Inhibition 9.0 pKd 19
pKd 9.0 (Kd 1x10-9 M) [19]
crenolanib Hs Inhibition 8.5 pKd 12
pKd 8.5 (Kd 3.2x10-9 M) [12]
quizartinib Hs Inhibition 8.1 pKd 4
pKd 8.1 (Kd 7.7x10-9 M) [4]
sunitinib Hs Inhibition 8.1 pKi 22
pKi 8.1 (Ki 8x10-9 M) [22]
PD166285 Hs Inhibition 7.0 pKi 27
pKi 7.0 (Ki 9.83x10-8 M) [27]
CP-673451 Hs Inhibition 9.0 pIC50 30
pIC50 9.0 (IC50 1x10-9 M) [30]
compound 8h [PMID: 22765894] Hs Inhibition 8.9 pIC50 17
pIC50 8.9 (IC50 1.3x10-9 M) [17]
SU11652 Hs Inhibition 8.5 pIC50 32
pIC50 8.5 (IC50 3x10-9 M) [32]
SU-14813 Hs Inhibition 8.4 pIC50 28
pIC50 8.4 (IC50 4x10-9 M) [28]
famitinib Hs Inhibition 8.4 pIC50 5
pIC50 8.4 (IC50 4x10-9 M) [5]
PDGF receptor tyrosine kinase inhibitor IV Hs Inhibition 8.4 pIC50 14
pIC50 8.4 (IC50 4.2x10-9 M) [14]
cediranib Hs Inhibition 8.3 pIC50 34
pIC50 8.3 (IC50 5x10-9 M) [34]
sunitinib Hs Inhibition 8.2 pIC50 18
pIC50 8.2 (IC50 5.7x10-9 M) [18]
lucitanib Hs Inhibition 8.1 pIC50 37
pIC50 8.1 (IC50 8x10-9 M) [37]
dovitinib Hs Inhibition 7.6 – 8.3 pIC50 29,33
pIC50 7.6 – 8.3 (IC50 2.7x10-8 – 5x10-9 M) [29,33]
PDGF RTK inhibitor Hs Inhibition 7.9 pIC50 8
pIC50 7.9 (IC50 1.2x10-8 M) [8]
Description: Inhibition of PDGFR autophosphorylation in human G292 cells
MK-2461 Hs Inhibition 7.7 pIC50 26
pIC50 7.7 (IC50 2.2x10-8 M) [26]
orantinib Hs Inhibition 7.3 pIC50 15
pIC50 7.3 (IC50 5x10-8 M) [15]
sorafenib Mm Inhibition 7.2 pIC50 35
pIC50 7.2 (IC50 5.7x10-8 M) [35]
nintedanib Hs Inhibition 7.2 pIC50 13
pIC50 7.2 (IC50 6.5x10-8 M) [13]
linifanib Hs Inhibition 7.2 pIC50 1
pIC50 7.2 (IC50 6.6x10-8 M) [1]
PDGF receptor tyrosine kinase inhibitor III Hs Inhibition 7.1 pIC50 21
pIC50 7.1 (IC50 8x10-8 M) [21]
pazopanib Hs Inhibition 7.1 pIC50 11
pIC50 7.1 (IC50 8.4x10-8 M) [11]
AGL 2043 Hs Inhibition 7.1 pIC50 10
pIC50 7.1 (IC50 9x10-8 M) [10]
Description: Using purified human PDGFRβ
Flt-3 inhibitor II Hs Inhibition 6.8 pIC50 20
pIC50 6.8 (IC50 1.71x10-7 M) [20]
tandutinib Hs Inhibition 6.7 pIC50 16
pIC50 6.7 (IC50 2x10-7 M) [16]
Ki-20227 Hs Inhibition 6.7 pIC50 25
pIC50 6.7 (IC50 2.17x10-7 M) [25]
vatalanib Hs Inhibition 6.2 pIC50 3
pIC50 6.2 (IC50 6x10-7 M) [3]
semaxanib Hs Inhibition 6.2 pIC50 3
pIC50 6.2 (IC50 6.8x10-7 M) [3]
masitinib Hs Inhibition 6.1 pIC50 7
pIC50 6.1 (IC50 8x10-7 M) [7]
GTP-14564 Hs Inhibition 6.0 pIC50 23
pIC50 6.0 (IC50 1x10-6 M) [23]
View species-specific inhibitor tables
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: 6,36

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 10.1 pKd
SU-14813 Hs Inhibitor Inhibition 9.5 pKd
Ki-20227 Hs Inhibitor Inhibition 9.5 pKd
cediranib Hs Inhibitor Inhibition 9.5 pKd
axitinib Hs Inhibitor Inhibition 9.2 pKd
dasatinib Hs Inhibitor Inhibition 9.2 pKd
foretinib Hs Inhibitor Inhibition 9.0 pKd
PD-173955 Hs Inhibitor Inhibition 8.9 pKd
staurosporine Hs Inhibitor Inhibition 8.7 pKd
linifanib Hs Inhibitor Inhibition 8.7 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: 2,9

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; IBGC4
OMIM: 615007
Disease:  Bilateral striopallidodentate calcinosis
Orphanet: ORPHA1980
References:  24
Disease:  Chronic myelomonocytic leukemia
Orphanet: ORPHA98823
Disease:  Myeloid neoplasm associated with PDGFRB rearrangement
Orphanet: ORPHA168950
Disease:  Myeloproliferative disorder, chronic, with eosinophilia
OMIM: 131440
Disease:  Myofibromatosis, infantile, 1
OMIM: 228550
Orphanet: ORPHA2591
Disease:  Unclassified chronic myeloproliferative disease
Orphanet: ORPHA86830

References

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4. Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, Gunawardane RN, Cramer MD, Gardner MF, James J et al.. (2009) Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J. Med. Chem.52 (23): 7808-16. [PMID:19754199]

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8. 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]

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13. 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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15. 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]

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19. Liu G, Campbell BT, Holladay MW, Ford Pulido JM, Hua H, Gitnick D, Gardner MF, James J, Breider MA, Brigham D et al.. (2012) Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett3 (12): 997-1002. [PMID:24900421]

20. 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]

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22. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB et al.. (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res.9 (1): 327-37. [PMID:12538485]

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26. 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]

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How to cite this page

Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: platelet-derived growth factor receptor, beta polypeptide. Last modified on 09/03/2015. Accessed on 30/08/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1804.