platelet derived growth factor receptor alpha | Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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platelet derived growth factor receptor alpha

Target not currently curated in GtoImmuPdb

Target id: 1803

Nomenclature: platelet derived growth factor receptor alpha

Abbreviated Name: PDGFRα

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 1089 4q12 PDGFRA platelet derived growth factor receptor alpha
Mouse 1 1089 5 Pdgfra platelet derived growth factor receptor, alpha polypeptide
Rat 1 1088 14p11 Pdgfra platelet derived growth factor receptor alpha
Previous and Unofficial Names
CD140a | PDGFR2 | APDGFR | PDGFACE | PDGFR-alpha | platelet-derived growth factor receptor, alpha polypeptide | platelet derived growth factor receptor, alpha polypeptide | platelet derived growth factor receptor
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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 Value Parameter Reference
AC710 Hs Inhibition 8.9 pKd 11
pKd 8.9 (Kd 1.3x10-9 M) [11]
crenolanib Hs Inhibition 8.7 pKd 8
pKd 8.7 (Kd 2.1x10-9 M) [8]
quizartinib Hs Inhibition 8.0 pKd 3
pKd 8.0 (Kd 1.1x10-8 M) [3]
CS2164 Hs Inhibition 9.0 pIC50 23
pIC50 9.0 (IC50 1x10-9 M) [23]
Description: Inhibition in a biochemical assay.
compound 8h [PMID: 21561767] Hs Inhibition 8.9 pIC50 17
pIC50 8.9 (IC50 1.3x10-9 M) [17]
PP121 Hs Inhibition 8.7 pIC50 2
pIC50 8.7 (IC50 2x10-9 M) [2]
compound 8i [PMID: 22765894] Hs Inhibition 8.7 pIC50 10
pIC50 8.7 (IC50 2x10-9 M) [10]
compound 8h [PMID: 22765894] Hs Inhibition 8.5 pIC50 10
pIC50 8.5 (IC50 3x10-9 M) [10]
CP-673451 Hs Inhibition 8.0 pIC50 16
pIC50 8.0 (IC50 1x10-8 M) [16]
ilorasertib Hs Inhibition 8.0 pIC50 7
pIC50 8.0 (IC50 1.1x10-8 M) [7]
Description: Measuring inhibition of kinase activity in a biochemical assay.
lucitanib Hs Inhibition 7.9 pIC50 22
pIC50 7.9 (IC50 1.3x10-8 M) [22]
CHMFL-KIT-64 Hs Inhibition 7.6 pIC50 21
pIC50 7.6 (IC50 2.5x10-8 M) [21]
Description: In a biochemical assay.
sitravatinib Hs Inhibition 7.5 pIC50 14
pIC50 7.5 (IC50 3x10-8 M) [14]
Description: In a biochemical enzyme activity assay.
cediranib Hs Inhibition 7.4 pIC50 19
pIC50 7.4 (IC50 3.6x10-8 M) [19]
ENMD-2076 Hs Inhibition 7.3 pIC50 15
pIC50 7.3 (IC50 5.6x10-8 M) [15]
nintedanib Hs Inhibition 7.2 pIC50 9
pIC50 7.2 (IC50 5.9x10-8 M) [9]
dovitinib Hs Inhibition 6.7 pIC50 18
pIC50 6.7 (IC50 2.1x10-7 M) [18]
masitinib Hs Inhibition 6.3 pIC50 5
pIC50 6.3 (IC50 5.4x10-7 M) [5]
PDGF receptor tyrosine kinase inhibitor II Mm Inhibition 6.0 pIC50 13
pIC50 6.0 (IC50 1.1x10-6 M) [13]
Description: Inhibition of PDGFR in intact Swiss 3T3 fibroblasts
View species-specific inhibitor tables
Inhibitor Comments
We have mapped PDGF receptor tyrosine kinase inhibitor II to the alpha subunit of the PDGFR [13], but as the experiments were carried out in intact cells, it is impossible to specify which subunit/s are involved in this interaction.
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
olaratumab Hs Binding 10.4 pKd 12
pKd 10.4 (Kd 4x10-11 M) [12]
Description: BIAcore assay
olaratumab Hs Binding 9.2 pIC50 12
pIC50 9.2 (IC50 5.8x10-10 M) [12]
Description: Cellular assay
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: 4,20

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRA
Ligand Sp. Type Action Value Parameter
cediranib Hs Inhibitor Inhibition 9.4 pKd
dasatinib Hs Inhibitor Inhibition 9.3 pKd
Ki-20227 Hs Inhibitor Inhibition 9.3 pKd
axitinib Hs Inhibitor Inhibition 9.3 pKd
sunitinib Hs Inhibitor Inhibition 9.1 pKd
SU-14813 Hs Inhibitor Inhibition 9.0 pKd
tandutinib Hs Inhibitor Inhibition 8.6 pKd
linifanib Hs Inhibitor Inhibition 8.4 pKd
foretinib Hs Inhibitor Inhibition 8.4 pKd
pazopanib Hs Inhibitor Inhibition 8.3 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: 1,6

Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRα/PDGFRa
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
masitinib Hs Inhibitor Inhibition 1.6
dasatinib Hs Inhibitor Inhibition 1.8
staurosporine Hs Inhibitor Inhibition 2.1 5.5 0.5
dorsomorphin Hs Inhibitor Inhibition 3.7 24.0 3.0
imatinib Hs Inhibitor Inhibition 5.9
sorafenib Hs Inhibitor Inhibition 7.8
sunitinib Hs Inhibitor Inhibition 10.9
tandutinib Hs Inhibitor Inhibition 11.1
PDGF RTK inhibitor Hs Inhibitor Inhibition 12.5 7.0 2.0
dovitinib Hs Inhibitor Inhibition 12.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Gastrointestinal stromal tumor
Disease Ontology: DOID:9253
OMIM: 606764
Orphanet: ORPHA44890
Comments: 
Disease:  Hypereosinophilic syndrome, idiopathic; HES
Synonyms: Hypereosinophilic syndrome of undetermined significance [Orphanet: ORPHA3260]
OMIM: 607685
Orphanet: ORPHA3260
Disease:  Myeloid neoplasm associated with PDGFRA rearrangement
Orphanet: ORPHA168947
Disease:  Precursor B-cell acute lymphoblastic leukemia
Synonyms: Acute lymphocytic leukemia [Disease Ontology: DOID:9952]
Leukemia, acute lymphoblastic; ALL [OMIM: 613065]
Leukemia, B-cell acute lymphoblastic, susceptibility to [OMIM: 613065]
Disease Ontology: DOID:9952
OMIM: 613065
Orphanet: ORPHA99860

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. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. (2008) Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat. Chem. Biol., 4 (11): 691-9. [PMID:18849971]

3. 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]

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 ONE, 4 (9): e7258. [PMID:19789626]

6. 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]

7. Glaser KB, Li J, Marcotte PA, Magoc TJ, Guo J, Reuter DR, Tapang P, Wei RQ, Pease LJ, Bui MH et al.. (2012) Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J. Pharmacol. Exp. Ther., 343 (3): 617-27. [PMID:22935731]

8. 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]

9. 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]

10. Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR et al.. (2012) The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett., 22 (15): 4979-85. [PMID:22765894]

11. 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 Lett, 3 (12): 997-1002. [PMID:24900421]

12. Loizos N, Huber J. (2012) Antibodies against PDGFRa. Patent number: US8128929. Assignee: Imclone Llc. Priority date: 17/06/2006. Publication date: 06/04/2012.

13. Mahboobi S, Teller S, Pongratz H, Hufsky H, Sellmer A, Botzki A, Uecker A, Beckers T, Baasner S, Schächtele C et al.. (2002) Bis(1H-2-indolyl)methanones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase. J. Med. Chem., 45 (5): 1002-18. [PMID:11855980]

14. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 7 (4): 4093-109. [PMID:26675259]

15. Pollard JR, Mortimore M. (2009) Discovery and development of aurora kinase inhibitors as anticancer agents. J. Med. Chem., 52 (9): 2629-51. [PMID:19320489]

16. Roberts WG, Whalen PM, Soderstrom E, Moraski G, Lyssikatos JP, Wang HF, Cooper B, Baker DA, Savage D, Dalvie D et al.. (2005) Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res., 65 (3): 957-66. [PMID:15705896]

17. Thomas M, Huang WS, Wen D, Zhu X, Wang Y, Metcalf CA, Liu S, Chen I, Romero J, Zou D et al.. (2011) Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg. Med. Chem. Lett., 21 (12): 3743-8. [PMID:21561767]

18. 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. Blood, 105 (7): 2941-8. [PMID:15598814]

19. 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]

20. 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]

21. Wu Y, Wang B, Wang J, Qi S, Zou F, Qi Z, Liu F, Liu Q, Chen C, Hu C et al.. (2019) Discovery of 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)acetamide (CHMFL-KIT-64) as a Novel Orally Available Potent Inhibitor against Broad-Spectrum Mutants of c-KIT Kinase for Gastrointestinal Stromal Tumors. J. Med. Chem., 62 (13): 6083-6101. [PMID:31250638]

22. 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]

23. Zhou Y, Shan S, Li ZB, Xin LJ, Pan DS, Yang QJ, Liu YP, Yue XP, Liu XR, Gao JZ et al.. (2017) CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency. Cancer Sci., 108 (3): 469-477. [PMID:28004478]

How to cite this page

Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: platelet derived growth factor receptor alpha. Last modified on 04/09/2019. Accessed on 11/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1803.