Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTI7421)

• DTT Name: Platelet-derived growth factor receptor beta (PDGFRB)
• Synonyms: Platelet-derived growth factor receptor 1; PDGFR1; PDGFR-beta; PDGFR-1; PDGFR; PDGF-R-beta; CD140b antigen; CD140b; CD140 antigen-like family member B; Beta-type platelet-derived growth factor receptor; Beta-PDGFR; Beta platelet-derived growth factor receptor
• Gene Name: PDGFRB
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: PGFRB_HUMAN
• TTD ID: T59102
• EC Number: EC 2.7.10.1
• Sequence:
  MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPV
  VWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFV
  PDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFS
  GIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGN
  EVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDH
  QDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDS
  SAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVL
  ELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNV
  TYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILA
  LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQL
  VLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGP
  HLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNAL
  PVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVP
  SAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLV
  KICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLG
  GTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLER
  LLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDND
  YIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQV
  EPEPELEQLPDSGCPAPRAEAEDSFL
• Function: Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -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 PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. 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. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. 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 cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  Cytokine-cytokine receptor interaction (hsa04060)
  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

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[2]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[1]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[3]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[7]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[8]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]

4 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25656651-Compound-21a	DMCKAON	N. A.	N. A.	Patented	[10]
PMID25656651-Compound-21b	DMVABXI	N. A.	N. A.	Patented	[10]
PMID28460551-Compound-2	DM4DOUB	N. A.	N. A.	Patented	[11]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[12]

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CDP-860	DMEI0LJ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[13]
SRI-62-834	DMRKE9G	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[14]
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]

106 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	[17]
(1H-indol-2-yl)(5-phenoxy-1H-indol-2-yl)methanone	DM94XJ2	Discovery agent	N.A.	Investigative	[17]
(1H-indol-2-yl)(6-methoxy-1H-indol-2-yl)methanone	DM7KDNM	Discovery agent	N.A.	Investigative	[17]
(2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamine	DMNGEFS	Discovery agent	N.A.	Investigative	[18]
(5-fluoro-1H-indol-2-yl)-(1H-indol-2-yl)methanone	DMIV4BU	Discovery agent	N.A.	Investigative	[17]
(5-hydroxy-1H-indol-2-yl)(1H-indol-2-yl)methanone	DMPBNYM	Discovery agent	N.A.	Investigative	[17]
(benzo[b]furan-2-yl)-(1H-indol-2-yl)methanone	DME80RK	Discovery agent	N.A.	Investigative	[15]
1-Phenyl-1H-benzoimidazol-5-ol	DMGV6BI	Discovery agent	N.A.	Investigative	[19]
1-Phenyl-1H-benzoimidazole	DM8YPH0	Discovery agent	N.A.	Investigative	[19]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[20]
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-dimethylamino-benzylidenyl)-2-indolinone	DM6XC0M	Discovery agent	N.A.	Investigative	[21]
3-(4-Fluoro-phenyl)-6,7-dimethoxy-quinoline	DM0POH2	Discovery agent	N.A.	Investigative	[16]
3-(6,7-Dimethoxy-quinolin-4-yloxy)-phenol	DM4DFUS	Discovery agent	N.A.	Investigative	[22]
3-(6,7-Dimethoxy-quinolin-4-yloxy)-phenylamine	DMAWXV6	Discovery agent	N.A.	Investigative	[22]
3-Benzimidazol-2-ylhydroquinolin-2-one	DMQXJA1	Discovery agent	N.A.	Investigative	[23]
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	[24]
3-Pyridin-4-yl-quinoline	DM6U074	Discovery agent	N.A.	Investigative	[24]
3-Pyridin-4-yl-quinoline-5,7-diol	DMPCT0A	Discovery agent	N.A.	Investigative	[24]
3-Thiophen-3-yl-quinoline	DM9MFZ1	Discovery agent	N.A.	Investigative	[16]
4-(2,3-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline	DM6PMFJ	Discovery agent	N.A.	Investigative	[22]
4-(3,4-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline	DMW1H6C	Discovery agent	N.A.	Investigative	[22]
4-(3,5-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline	DM5279R	Discovery agent	N.A.	Investigative	[22]
4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinazoline	DMNBLQ8	Discovery agent	N.A.	Investigative	[22]
4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinoline	DMK6JV7	Discovery agent	N.A.	Investigative	[22]
4-(3-Ethoxy-phenoxy)-6,7-dimethoxy-quinoline	DMOQE5W	Discovery agent	N.A.	Investigative	[22]
4-(3-Ethyl-phenoxy)-6,7-dimethoxy-quinoline	DMFM9SH	Discovery agent	N.A.	Investigative	[22]
4-(3-Fluoro-phenoxy)-6,7-dimethoxy-quinoline	DMER3D9	Discovery agent	N.A.	Investigative	[22]
4-(5-Methoxy-benzoimidazol-1-yl)-phenylamine	DMIWT60	Discovery agent	N.A.	Investigative	[25]
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	[19]
5,6,7-Trimethoxy-3-pyridin-4-yl-quinoline	DM53CLY	Discovery agent	N.A.	Investigative	[24]
5,7-Dimethoxy-3-pyridin-4-yl-quinoline	DM724JF	Discovery agent	N.A.	Investigative	[24]
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-Methoxy-1-phenyl-1H-benzoimidazole	DMPEKWD	Discovery agent	N.A.	Investigative	[19]
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-(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	[24]
6,7-Dimethoxy-3-thiophen-2-yl-quinoline	DM6WD8T	Discovery agent	N.A.	Investigative	[16]
6,7-Dimethoxy-4-(2-methoxy-phenoxy)-quinoline	DMU15YV	Discovery agent	N.A.	Investigative	[22]
6,7-Dimethoxy-4-(3-methoxy-phenoxy)-quinoline	DMPS2GX	Discovery agent	N.A.	Investigative	[22]
6,7-Dimethoxy-4-(3-nitro-phenoxy)-quinoline	DM3YSNX	Discovery agent	N.A.	Investigative	[22]
6,7-Dimethoxy-4-(4-methoxy-phenoxy)-quinoline	DMX2VFP	Discovery agent	N.A.	Investigative	[22]
6,7-Dimethoxy-4-m-tolyloxy-quinoline	DMEMGPU	Discovery agent	N.A.	Investigative	[22]
6,7-Dimethoxy-4-phenoxy-quinoline	DMBZP3I	Discovery agent	N.A.	Investigative	[22]
6-Methoxy-3-pyridin-4-yl-quinoline	DM52SDO	Discovery agent	N.A.	Investigative	[24]
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	[24]
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	[24]
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]
AGL 2043	DMM9A5N	Discovery agent	N.A.	Investigative	[26]
Benzyl-(6,7-dimethoxy-quinolin-3-yl)-amine	DMFTIMS	Discovery agent	N.A.	Investigative	[16]
Bis(5-acetoxybenzo[b]furan-2-yl)methanone	DM36VKH	Discovery agent	N.A.	Investigative	[15]
Bis(5-aminobenzo[b]furan-2-yl)methanone	DMHRGTY	Discovery agent	N.A.	Investigative	[15]
Bis(5-hydroxybenzo[b]furan-2-yl)methanone	DMGRKDP	Discovery agent	N.A.	Investigative	[15]
Bis(5-methoxybenzo[b]furan-2-yl)methanone	DM9XC6A	Discovery agent	N.A.	Investigative	[15]
Bis(6-hydroxybenzo[b]furan-2-yl)methanone	DMRGNSQ	Discovery agent	N.A.	Investigative	[15]
Bis(benzo[b]furan-2-yl)methanone	DMK2ZG4	Discovery agent	N.A.	Investigative	[15]
Bis-(5-hydroxy-1H-indol-2-yl)-methanone	DMTSEXB	Discovery agent	N.A.	Investigative	[17]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[27]
CP-673451	DMVBPRO	Discovery agent	N.A.	Investigative	[28]
Di(1H-indol-2-yl)methanone	DM3DR6J	Discovery agent	N.A.	Investigative	[17]
GTP-14564	DMW23Y9	Discovery agent	N.A.	Investigative	[29]
HKI-9924129	DM5LR2B	Gram-positive bacterial infection	1B74-1G40	Investigative	[30]
JNJ-10198409	DM9GDP5	Discovery agent	N.A.	Investigative	[18]
Ki-11502	DMLG2EA	Discovery agent	N.A.	Investigative	[31]
Ki-20227	DM9M3VC	Discovery agent	N.A.	Investigative	[32]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[30]
PD-0173952	DMSCQ9U	Discovery agent	N.A.	Investigative	[30]
PD-0173955	DMOZEW9	Discovery agent	N.A.	Investigative	[30]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[30]
PD-0173958	DMZQ8YV	Discovery agent	N.A.	Investigative	[30]
PD-0179483	DMKO8LE	Discovery agent	N.A.	Investigative	[30]
PDGF receptor tyrosine kinase inhibitor III	DMORLTH	Discovery agent	N.A.	Investigative	[33]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[34]
Ro-4396686	DM5DMCH	Discovery agent	N.A.	Investigative	[35]
RPR-101511	DM0HD3O	Discovery agent	N.A.	Investigative	[16]
RPR-108514A	DM37I92	Discovery agent	N.A.	Investigative	[36]
SU-11652	DMGQXN7	Discovery agent	N.A.	Investigative	[1]
TG-100435	DMIR3X2	Discovery agent	N.A.	Investigative	[37]
XB-387	DMBN7UX	Non-small-cell lung cancer	2C25.Y	Investigative	[38]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	5.35E-10	0.36	0.89
Renal cancer	2C82	Kidney	4.13E-01	0.06	0.16
Myelodysplastic syndrome	2C82	Bone marrow	1.18E-01	0.09	0.32
Breast cancer	2C82	Breast tissue	1.76E-12	-0.49	-0.55
Acute myelocytic leukaemia	2C82	Bone marrow	3.56E-02	0.07	0.27
Head and neck cancer	2C82	Head and neck tissue	1.95E-31	1.69	1.65
Lung cancer	2C82	Lung tissue	4.17E-40	-0.57	-1.3

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