Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8FYO9)

• DTT Name: Platelet-derived growth factor receptor alpha (PDGFRA)
• Synonyms: RHEPDGFRA; Platelet-derived growth factor receptor 2; Platelet-derived growth factor alpha receptor; PDGFR2; PDGFR-alpha; PDGFR-2; PDGF-R-alpha; CD140a antigen; CD140a; CD140 antigen-like family member A; Alpha-type platelet-derived growth factor receptor; Alpha platelet-derived growth factor receptor
• Gene Name: PDGFRA
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: PGFRA_HUMAN
• TTD ID: T53524
• EC Number: EC 2.7.10.1
• Sequence:
  MGTSHPAFLVLGCLLTGLSLILCQLSLPSILPNENEKVVQLNSSFSLRCFGESEVSWQYP
  MSEEESSDVEIRNEENNSGLFVTVLEVSSASAAHTGLYTCYYNHTQTEENELEGRHIYIY
  VPDPDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYDSRQGFNG
  TFTVGPYICEATVKGKKFQTIPFNVYALKATSELDLEMEALKTVYKSGETIVVTCAVFNN
  EVVDLQWTYPGEVKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVK
  EMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEVRAYPPPRISWLKNNLTLIENL
  TEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDL
  VDDHHGSTGGQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRD
  RSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAPTLRSELTVAAAVLVLLVIVII
  SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLG
  SGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNL
  LGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSY
  VILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKN
  LLSDDNSEGLTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLA
  RDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMM
  VDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKK
  SYEKIHLDFLKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYII
  PLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTFIKREDETIEDIDMMDDIGIDS
  SDLVEDSFL
• Function: Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  Cytokine-cytokine receptor interaction (hsa04060)
  Endocytosis (hsa04144)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Gap junction (hsa04540)
  Regulation of actin cytoskeleton (hsa04810)
  HTLV-I infection (hsa05166)
  Pathways in cancer (hsa05200)
  MicroRNAs in cancer (hsa05206)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[2]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[3]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[4]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[1]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[5]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[6]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[7]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[8]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]

6 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID28460551-Compound-1	DMHV75N	Breast cancer	2C60-2C65	Patented	[11]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[12]
Pyridine derivative 19	DMXYT40	N. A.	N. A.	Patented	[12]
Pyridine derivative 20	DMAOF0W	N. A.	N. A.	Patented	[12]
Pyridine derivative 21	DMF3907	N. A.	N. A.	Patented	[12]
Pyridine derivative 22	DMSIERF	N. A.	N. A.	Patented	[12]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SRI-62-834	DMRKE9G	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[13]
CEP-2563	DMH1PQ0	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[14]
AG1295	DMT10C2	N. A.	N. A.	Terminated	[15]
RG-13022	DMRFYOS	N. A.	N. A.	Terminated	[16]

79 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1H-indol-2-yl)(5-methoxy-1H-indol-2-yl)methanone	DM21CXZ	Discovery agent	N.A.	Investigative	[15]
(1H-indol-2-yl)(5-phenoxy-1H-indol-2-yl)methanone	DM94XJ2	Discovery agent	N.A.	Investigative	[15]
(1H-indol-2-yl)(6-methoxy-1H-indol-2-yl)methanone	DM7KDNM	Discovery agent	N.A.	Investigative	[15]
(5-fluoro-1H-indol-2-yl)-(1H-indol-2-yl)methanone	DMIV4BU	Discovery agent	N.A.	Investigative	[15]
(5-hydroxy-1H-indol-2-yl)(1H-indol-2-yl)methanone	DMPBNYM	Discovery agent	N.A.	Investigative	[15]
1-Phenyl-1H-benzoimidazol-5-ol	DMGV6BI	Discovery agent	N.A.	Investigative	[17]
1-Phenyl-1H-benzoimidazole	DM8YPH0	Discovery agent	N.A.	Investigative	[17]
3-((E)-Styryl)-quinoline	DMAO64J	Discovery agent	N.A.	Investigative	[16]
3-(1H-Indol-3-yl)-6,7-dimethoxy-quinoline	DMSGCKU	Discovery agent	N.A.	Investigative	[16]
3-(1H-Indol-3-yl)-quinoline	DMW7XN5	Discovery agent	N.A.	Investigative	[16]
3-(2-Cyclohexyl-ethyl)-6,7-dimethoxy-quinoline	DMVUK96	Discovery agent	N.A.	Investigative	[16]
3-(3,4-Dichloro-phenyl)-6,7-dimethoxy-quinoline	DMEJH13	Discovery agent	N.A.	Investigative	[16]
3-(3,4-Difluoro-phenyl)-6,7-dimethoxy-quinoline	DMX3AMB	Discovery agent	N.A.	Investigative	[16]
3-(3,4-Dimethoxy-phenyl)-6,7-dimethoxy-quinoline	DMDU10A	Discovery agent	N.A.	Investigative	[16]
3-(3-Fluoro-phenyl)-6,7-dimethoxy-quinoline	DM0ZHJQ	Discovery agent	N.A.	Investigative	[16]
3-(4-Fluoro-phenyl)-6,7-dimethoxy-quinoline	DM0POH2	Discovery agent	N.A.	Investigative	[16]
3-Benzyloxy-6,7-dimethoxy-quinoline	DMPG315	Discovery agent	N.A.	Investigative	[16]
3-Cyclohexylethynyl-6,7-dimethoxy-quinoline	DMCQ6J8	Discovery agent	N.A.	Investigative	[16]
3-Cyclopent-1-enyl-6,7-dimethoxy-quinoline	DM1FSZM	Discovery agent	N.A.	Investigative	[16]
3-Cyclopentyl-6,7-dimethoxy-quinoline	DMS7B6T	Discovery agent	N.A.	Investigative	[16]
3-Pyridin-3-yl-quinoline-6,7-diol	DM60Q1B	Discovery agent	N.A.	Investigative	[16]
3-Pyridin-4-yl-quinolin-7-ol	DM0SEL5	Discovery agent	N.A.	Investigative	[18]
3-Pyridin-4-yl-quinoline	DM6U074	Discovery agent	N.A.	Investigative	[18]
3-Pyridin-4-yl-quinoline-5,7-diol	DMPCT0A	Discovery agent	N.A.	Investigative	[18]
3-Thiophen-3-yl-quinoline	DM9MFZ1	Discovery agent	N.A.	Investigative	[16]
4-(3,4-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline	DMW1H6C	Discovery agent	N.A.	Investigative	[19]
4-(5-Methoxy-benzoimidazol-1-yl)-phenylamine	DMIWT60	Discovery agent	N.A.	Investigative	[20]
4-(6,7-Dimethoxy-quinolin-3-yl)-benzoic acid	DM8A6UH	Discovery agent	N.A.	Investigative	[16]
4-(6,7-Dimethoxy-quinolin-3-yl)-phenol	DM9RNUX	Discovery agent	N.A.	Investigative	[16]
4-Benzoimidazol-1-yl-phenylamine	DM7AOGD	Discovery agent	N.A.	Investigative	[17]
5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol	DMWSLTB	Discovery agent	N.A.	Investigative	[21]
5,6,7-Trimethoxy-3-pyridin-4-yl-quinoline	DM53CLY	Discovery agent	N.A.	Investigative	[18]
5,7-Dimethoxy-3-pyridin-4-yl-quinoline	DM724JF	Discovery agent	N.A.	Investigative	[18]
5,7-Dimethoxy-3-thiophen-3-yl-quinoline	DMJAQ41	Discovery agent	N.A.	Investigative	[16]
5,7-Dimethyl-3-thiophen-3-yl-quinoline	DM3P79O	Discovery agent	N.A.	Investigative	[16]
5-(6,7-Dimethoxy-quinolin-3-yl)-1H-pyridin-2-one	DMVMBG0	Discovery agent	N.A.	Investigative	[16]
5-Fluoro-3-thiophen-3-yl-quinoline	DM0OQTJ	Discovery agent	N.A.	Investigative	[16]
5-Methoxy-1-phenyl-1H-benzoimidazole	DMPEKWD	Discovery agent	N.A.	Investigative	[17]
6,7-Dichloro-3-thiophen-3-yl-quinoline	DMJNHSL	Discovery agent	N.A.	Investigative	[16]
6,7-Difluoro-3-thiophen-3-yl-quinoline	DMUZYXQ	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-((E)-styryl)-quinoline	DMSM0QV	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-(2-methoxy-phenyl)-quinoline	DMPYGK9	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-(3-methoxy-phenyl)-quinoline	DMDENVF	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-(4-methoxy-phenyl)-quinoline	DM12DVT	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-(4-nitro-phenyl)-quinoline	DMM7NHI	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-p-tolyl-quinoline	DMM7IAK	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-phenyl-quinoline	DM516B4	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-phenylethynyl-quinoline	DMFRXDT	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-pyridin-3-yl-quinoline	DMSG1AY	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-3-pyridin-4-yl-quinoline	DMW7K5P	Discovery agent	N.A.	Investigative	[18]
6,7-Dimethoxy-3-thiophen-2-yl-quinoline	DM6WD8T	Discovery agent	N.A.	Investigative	[16]
6-Methoxy-3-pyridin-4-yl-quinoline	DM52SDO	Discovery agent	N.A.	Investigative	[18]
6-Methoxy-3-thiophen-3-yl-quinoline	DMOYL71	Discovery agent	N.A.	Investigative	[16]
7-Chloro-3-pyridin-4-yl-quinoline	DM53A1R	Discovery agent	N.A.	Investigative	[18]
7-Fluoro-3-thiophen-3-yl-quinoline	DM0QI8V	Discovery agent	N.A.	Investigative	[16]
7-Methoxy-3-pyridin-4-yl-quinoline	DMUZIDT	Discovery agent	N.A.	Investigative	[18]
7-Methoxy-3-thiophen-3-yl-quinoline	DM9QKLC	Discovery agent	N.A.	Investigative	[16]
7-Thiophen-3-yl-[1,3]dioxolo[4,5-g]quinoline	DMMU5SO	Discovery agent	N.A.	Investigative	[16]
Benzyl-(6,7-dimethoxy-quinolin-3-yl)-amine	DMFTIMS	Discovery agent	N.A.	Investigative	[16]
Bis-(5-hydroxy-1H-indol-2-yl)-methanone	DMTSEXB	Discovery agent	N.A.	Investigative	[15]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[22]
CP-673451	DMVBPRO	Discovery agent	N.A.	Investigative	[23]
D-65476	DM0A54V	Discovery agent	N.A.	Investigative	[24]
Di(1H-indol-2-yl)methanone	DM3DR6J	Discovery agent	N.A.	Investigative	[15]
HKI-9924129	DM5LR2B	Gram-positive bacterial infection	1B74-1G40	Investigative	[25]
JNJ-10198409	DM9GDP5	Discovery agent	N.A.	Investigative	[26]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[25]
PD-0173952	DMSCQ9U	Discovery agent	N.A.	Investigative	[25]
PD-0173955	DMOZEW9	Discovery agent	N.A.	Investigative	[25]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[25]
PD-0173958	DMZQ8YV	Discovery agent	N.A.	Investigative	[25]
PD-0179483	DMKO8LE	Discovery agent	N.A.	Investigative	[25]
PMID21561767C8h	DMABZH6	Discovery agent	N.A.	Investigative	[27]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[28]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[29]
Ro-4396686	DM5DMCH	Discovery agent	N.A.	Investigative	[30]
RPR-101511	DM0HD3O	Discovery agent	N.A.	Investigative	[16]
RPR-108514A	DM37I92	Discovery agent	N.A.	Investigative	[31]
SU-11652	DMGQXN7	Discovery agent	N.A.	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Gastric cancer	2C82	Gastric tissue	3.46E-01	-0.23	-1.55
Glioma	2C82	Brainstem tissue	4.48E-02	1.37	3.31
Glioma	2C82	White matter	9.98E-03	2.15	1.46
Ovarian cancer	2C82	Ovarian tissue	1.31E-03	-1.66	-1.59
Renal cancer	2C82	Kidney	1.48E-03	-0.38	-1.26

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