Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSNK9Q)

• DOT Name: Platelet-derived growth factor receptor beta (PDGFRB)
• Synonyms: PDGF-R-beta; PDGFR-beta; EC 2.7.10.1; Beta platelet-derived growth factor receptor; Beta-type platelet-derived growth factor receptor; CD140 antigen-like family member B; Platelet-derived growth factor receptor 1; PDGFR-1; CD antigen CD140b
• Gene Name: PDGFRB
• Related Disease:
  Acroosteolysis-keloid-like lesions-premature aging syndrome
  Myofibromatosis, infantile, 1
  Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome
  Basal ganglia calcification, idiopathic, 4
  Bilateral striopallidodentate calcinosis
  Infantile myofibromatosis
• UniProt ID: PGFRB_HUMAN
• PDB ID: 1GQ5; 1H9O; 1SHA; 2IUI; 2L6W; 2PLD; 2PLE; 3MJG
• EC Number: 2.7.10.1
• Pfam ID: PF00047 ; PF13927 ; PF07714
• Sequence:
  MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPV
  VWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFV
  PDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFS
  GIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGN
  EVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDH
  QDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDS
  SAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVL
  ELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNV
  TYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILA
  LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQL
  VLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGP
  HLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNAL
  PVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVP
  SAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLV
  KICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLG
  GTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLER
  LLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDND
  YIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQV
  EPEPELEQLPDSGCPAPRAEAEDSFL
• Function: Tyrosine-protein kinase that acts as a 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. 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.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  Phospholipase D sig.ling pathway (hsa04072)
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Gap junction (hsa04540)
  JAK-STAT sig.ling pathway (hsa04630)
  Regulation of actin cytoskeleton (hsa04810)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Downstream signal transduction (R-HSA-186763)
  Signaling by PDGF (R-HSA-186797)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acroosteolysis-keloid-like lesions-premature aging syndrome	DISA2X25	Definitive	Autosomal dominant	[1]
Myofibromatosis, infantile, 1	DIS7CJCY	Definitive	Autosomal dominant	[2]
Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome	DIS87WLW	Definitive	Autosomal dominant	[3]
Basal ganglia calcification, idiopathic, 4	DIS452BK	Strong	Autosomal dominant	[4]
Bilateral striopallidodentate calcinosis	DISNZJTB	Supportive	Autosomal dominant	[5]
Infantile myofibromatosis	DISXT8Z7	Supportive	Autosomal dominant	[6]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	Platelet-derived growth factor receptor beta (PDGFRB) increases the abundance of Glutathione.	[43]

6 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Platelet-derived growth factor receptor beta (PDGFRB).	[7]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the phosphorylation of Platelet-derived growth factor receptor beta (PDGFRB).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Platelet-derived growth factor receptor beta (PDGFRB).	[33]
AEW-541	DMQF982	Phase 1	AEW-541 decreases the phosphorylation of Platelet-derived growth factor receptor beta (PDGFRB).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the phosphorylation of Platelet-derived growth factor receptor beta (PDGFRB).	[36]
LXA4	DMGSVL0	Investigative	LXA4 decreases the phosphorylation of Platelet-derived growth factor receptor beta (PDGFRB).	[42]

32 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[17]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[18]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[19]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[20]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[21]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[22]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[23]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[24]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[26]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[28]
Masitinib	DMRSNEU	Phase 3	Masitinib decreases the activity of Platelet-derived growth factor receptor beta (PDGFRB).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[31]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[32]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[34]
PMID25656651-Compound-5	DMAI95U	Patented	PMID25656651-Compound-5 decreases the activity of Platelet-derived growth factor receptor beta (PDGFRB).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[39]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[40]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[40]
eucalyptol	DME5CK3	Investigative	eucalyptol decreases the expression of Platelet-derived growth factor receptor beta (PDGFRB).	[41]

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