Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCMZ0W8)

• DOT Name: Platelet-derived growth factor subunit A (PDGFA)
• Synonyms: PDGF subunit A; PDGF-1; Platelet-derived growth factor A chain; Platelet-derived growth factor alpha polypeptide
• Gene Name: PDGFA
• UniProt ID: PDGFA_HUMAN
• PDB ID: 3MJK
• Pfam ID: PF00341 ; PF04692
• Sequence:
  MRTLACLLLLGCGYLAHVLAEEAEIPREVIERLARSQIHSIRDLQRLLEIDSVGSEDSLD
  TSLRAHGVHATKHVPEKRPLPIRRKRSIEEAVPAVCKTRTVIYEIPRSQVDPTSANFLIW
  PPCVEVKRCTGCCNTSSVKCQPSRVHHRSVKVAKVEYVRKKPKLKEVQVRLEEHLECACA
  TTSLNPDYREEDTGRPRESGKKRKRKRLKPT
• 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 lung alveolar septum formation during embryogenesis, normal development of the gastrointestinal tract, normal development of Leydig cells and spermatogenesis. Required for normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFB.
• 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)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  MicroR.s in cancer (hsa05206)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Choline metabolism in cancer (hsa05231)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  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)
  NFE2L2 regulating tumorigenic genes (R-HSA-9818030)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Platelet-derived growth factor subunit A (PDGFA) increases the abundance of Dinoprostone.	[29]
Epoprostenol	DMUTYR2	Approved	Platelet-derived growth factor subunit A (PDGFA) increases the abundance of Epoprostenol.	[29]

2 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 A (PDGFA).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Platelet-derived growth factor subunit A (PDGFA).	[20]

36 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 A (PDGFA).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Platelet-derived growth factor subunit A (PDGFA).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Platelet-derived growth factor subunit A (PDGFA).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[15]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Platelet-derived growth factor subunit A (PDGFA).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[17]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[18]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[7]
Estriol	DMOEM2I	Approved	Estriol decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[7]
Ramipril	DM2R68E	Approved	Ramipril decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[15]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[10]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[23]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[25]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[26]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[27]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[28]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[27]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[21]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon increases the expression of Platelet-derived growth factor subunit A (PDGFA).	[27]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[21]
[3H]estrone-3-sulphate	DMGPF0N	Investigative	[3H]estrone-3-sulphate decreases the expression of Platelet-derived growth factor subunit A (PDGFA).	[7]

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