Top ▲

platelet derived growth factor receptor alpha

Click here for help

Target id: 1803

Nomenclature: platelet derived growth factor receptor alpha

Abbreviated Name: PDGFRα

Family: Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

Contents:

Gene and Protein Information Click here for help
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 39.55 cM Pdgfra platelet derived growth factor receptor, alpha polypeptide
Rat 1 1088 14p11 Pdgfra platelet derived growth factor receptor alpha
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P16234 (Hs), P26618 (Mm), P20786 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL2007 (Hs), CHEMBL3466 (Mm)
DrugBank Target P16234 (Hs)
Ensembl Gene ENSG00000134853 (Hs), ENSMUSG00000029231 (Mm), ENSRNOG00000002244 (Rn)
Entrez Gene 5156 (Hs), 18595 (Mm), 25267 (Rn)
Human Protein Atlas ENSG00000134853 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:5156 (Hs), mmu:18595 (Mm), rno:25267 (Rn)
OMIM 173490 (Hs)
Orphanet ORPHA124154 (Hs)
Pharos P16234 (Hs)
RefSeq Nucleotide NM_006206 (Hs), NM_001083316 (Mm), NM_012802 (Rn)
RefSeq Protein NP_006197 (Hs), NP_001076785 (Mm), NP_035188 (Mm), NP_036934 (Rn)
UniProtKB P16234 (Hs), P26618 (Mm), P20786 (Rn)
Wikipedia PDGFRA (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Endogenous ligands (Human)
PDGF

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AC710 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pKd 16
⤷ pKd 8.9 (Kd 1.3x10-9 M) [16]
crenolanib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pKd 10
⤷ pKd 8.7 (Kd 2.1x10-9 M) [10]
quizartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pKd 5
⤷ pKd 8.0 (Kd 1.1x10-8 M) [5]
toceranib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pKi 15
⤷ pKi 8.3 (Ki 5x10-9 M) [15]
ibcasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 28
⤷ pIC50 9.0 (IC50 1x10-9 M) [28]
Description: Inhibition in a biochemical assay.
compound 8h [PMID: 21561767] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.9 pIC50 22
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [22]
PP121 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 3
⤷ pIC50 8.7 (IC50 2x10-9 M) [3]
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 13
⤷ pIC50 8.7 (IC50 2x10-9 M) [13]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 13
⤷ pIC50 8.5 (IC50 3x10-9 M) [13]
elenestinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >8.4 pIC50 12
⤷ pIC50 >8.4 (IC50 <4.5x10-9 M) [12]
Description: Biochemical inhibition assay, using PDGFRαD842V
CP-673451 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 21
⤷ pIC50 8.0 (IC50 1x10-8 M) [21]
ilorasertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 9
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [9]
Description: Measuring inhibition of kinase activity in a biochemical assay.
lucitanib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 27
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [27]
CHMFL-KIT-64 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 26
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [26]
Description: In a biochemical assay.
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 19
⤷ pIC50 7.5 (IC50 3x10-8 M) [19]
Description: In a biochemical enzyme activity assay.
cediranib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 24
⤷ pIC50 7.4 (IC50 3.6x10-8 M) [24]
M4205 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 4
⤷ pIC50 7.3 (IC50 5x10-8 M) [4]
Description: Biochemical inhibitory potency
BPR1R024 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 14
⤷ pIC50 7.3 (IC50 5.27x10-8 M) [14]
ENMD-2076 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 20
⤷ pIC50 7.3 (IC50 5.6x10-8 M) [20]
nintedanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 11
⤷ pIC50 7.2 (IC50 5.9x10-8 M) [11]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 23
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [23]
masitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 7
⤷ pIC50 6.3 (IC50 5.4x10-7 M) [7]
vimseltinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <6.0 pIC50 1
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [1]
PDGF receptor tyrosine kinase inhibitor II Small molecule or natural product Primary target of this compound Mm Inhibition 6.0 pIC50 18
⤷ pIC50 6.0 (IC50 1.1x10-6 M) [18]
Description: Inhibition of PDGFR in intact Swiss 3T3 fibroblasts
seralutinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 29
⤷ [29]
View species-specific inhibitor tables
Inhibitor Comments
We have mapped PDGF receptor tyrosine kinase inhibitor II to the alpha subunit of the PDGFR [18], 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 Peptide Approved drug Primary target of this compound Hs Binding 10.4 pKd 17
⤷ pKd 10.4 (Kd 4x10-11 M) [17]
Description: BIAcore assay
olaratumab Peptide Approved drug Primary target of this compound Hs Binding 9.2 pIC50 17
⤷ pIC50 9.2 (IC50 5.8x10-10 M) [17]
Description: Cellular assay
DiscoveRx KINOMEscan® screen Click here for help
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: 6,25
Key to terms and symbols Click column headers to sort
Target used in screen: PDGFRA
Ligand Sp. Type Action Value Parameter
cediranib Small molecule or natural product Hs Inhibitor Inhibition 9.4 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.3 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 9.3 pKd
axitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 9.0 pKd
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 8.4 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
pazopanib Small molecule or natural product Approved drug 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 Click here for help
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: 2,8
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 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.6
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.8
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.1 5.5 0.5
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.7 24.0 3.0
imatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 10.9
tandutinib Small molecule or natural product Hs Inhibitor Inhibition 11.1
PDGF RTK inhibitor Small molecule or natural product Hs Inhibitor Inhibition 12.5 7.0 2.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 12.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Gastrointestinal stromal tumor
Disease Ontology: DOID:9253
OMIM: 606764
Orphanet: ORPHA44890
Comments:  A heterozygous mutation in PDGFRA is implicated in the somatic form of gastrointestinal tumors.
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

Show »

1. Ahn Y,Vogeti L, Caldwell TM, Kaufman MD, Flynn DL. (2014) 2-aminopyrimidin-6-ones and analogs exhibiting anti-cancer and anti-proliferative activities. Patent number: WO2014145025A2. Assignee: Deciphera Pharmaceuticals, Llc. Priority date: 15/03/2013. Publication date: 18/09/2014.

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. 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]

4. Blum A, Dorsch D, Linde N, Brandstetter S, Buchstaller HP, Busch M, Glaser N, Grädler U, Ruff A, Petersson C et al.. (2023) Identification of M4205─A Highly Selective Inhibitor of KIT Mutations for Treatment of Unresectable Metastatic or Recurrent Gastrointestinal Stromal Tumors. J Med Chem, 66 (4): 2386-2395. [PMID:36728508]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. Kim JL, Dineen TA, Guzi T. (2020) Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases. Patent number: WO2020210293A1. Assignee: Blueprint Medicines Corporation. Priority date: 08/04/2020. Publication date: 15/10/2020.

13. 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]

14. Lee KH, Yen WC, Lin WH, Wang PC, Lai YL, Su YC, Chang CY, Wu CS, Huang YC, Yang CM et al.. (2021) Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model. J Med Chem, 64 (19): 14477-14497. [PMID:34606263]

15. Liao AT, Chien MB, Shenoy N, Mendel DB, McMahon G, Cherrington JM, London CA. (2002) Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors. Blood, 100 (2): 585-93. [PMID:12091352]

16. 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]

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

18. 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]

19. 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]

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

21. 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]

22. 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]

23. 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]

24. 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]

25. 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]

26. 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]

27. 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]

28. 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]

29. Zisman LS. (2014) Non-selective kinase inhibitors. Patent number: WO2014110200A1. Assignee: Zisman LS. Priority date: 10/01/2013. Publication date: 17/07/2014.

How to cite this page

Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: platelet derived growth factor receptor alpha. Last modified on 03/02/2023. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1803.