Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMFMFC3)

• DOT Name: Platelet-derived growth factor subunit B (PDGFB)
• Synonyms: PDGF subunit B; PDGF-2; Platelet-derived growth factor B chain; Platelet-derived growth factor beta polypeptide; Proto-oncogene c-Sis; Becaplermin
• Gene Name: PDGFB
• Related Disease:
  Basal ganglia calcification, idiopathic, 5
  Bilateral striopallidodentate calcinosis
  Familial meningioma
• UniProt ID: PDGFB_HUMAN
• PDB ID: 1PDG; 3MJG; 4HQU; 4HQX; 4QCI; 6T9E
• Pfam ID: PF00341 ; PF04692
• Sequence:
  MNRCWALFLSLCCYLRLVSAEGDPIPEELYEMLSDHSIRSFDDLQRLLHGDPGEEDGAEL
  DLNMTRSHSGGELESLARGRRSLGSLTIAEPAMIAECKTRTEVFEISRRLIDRTNANFLV
  WPPCVEVQRCSGCCNNRNVQCRPTQVQLRPVQVRKIEIVRKKPIFKKATVTLEDHLACKC
  ETVAAARPVTRSPGGSQEQRAKTPQTRVTIRTVRVRRPPKGKHRKFKHTHDKTALKETLG
  A
• Function: Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA.
• Tissue Specificity: Expressed at high levels in the heart, brain (sustantia nigra), placenta and fetal kidney. Expressed at moderate levels in the brain (hippocampus), skeletal muscle, kidney and lung.
• 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)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Re.l cell carcinoma (hsa05211)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Choline metabolism in cancer (hsa05231)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  PIP3 activates AKT signaling (R-HSA-1257604)
  Downstream signal transduction (R-HSA-186763)
  Signaling by PDGF (R-HSA-186797)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Basal ganglia calcification, idiopathic, 5	DISQM83V	Strong	Autosomal dominant	[1]
Bilateral striopallidodentate calcinosis	DISNZJTB	Supportive	Autosomal dominant	[2]
Familial meningioma	DIS30G91	Limited	Autosomal dominant	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Morphine	DMRMS0L	Approved	Platelet-derived growth factor subunit B (PDGFB) decreases the response to substance of Morphine.	[29]

3 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 subunit B (PDGFB).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Platelet-derived growth factor subunit B (PDGFB).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Platelet-derived growth factor subunit B (PDGFB).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[6]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Platelet-derived growth factor subunit B (PDGFB).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[11]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[12]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[13]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Platelet-derived growth factor subunit B (PDGFB).	[14]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[15]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[16]
Ramipril	DM2R68E	Approved	Ramipril decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[19]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[20]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[20]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[23]
JWH-015	DMGTSCP	Patented	JWH-015 increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[9]
Taxifolin	DMQJSF9	Preclinical	Taxifolin decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[20]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[26]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[27]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Platelet-derived growth factor subunit B (PDGFB).	[20]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[22]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Platelet-derived growth factor subunit B (PDGFB).	[22]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
adenosine diphosphate	DMFUHKP	Investigative	adenosine diphosphate increases the secretion of Platelet-derived growth factor subunit B (PDGFB).	[28]

References

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