Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIM9MZ3)

• DOT Name: Vascular endothelial growth factor A, long form
• Synonyms: L-VEGF; Vascular permeability factor; VPF
• Gene Name: VEGFA
• UniProt ID: VEGFA_HUMAN
• PDB ID: 1BJ1 ; 1CZ8 ; 1FLT ; 1KAT ; 1KMX ; 1MJV ; 1MKG ; 1MKK ; 1QTY ; 1TZH ; 1TZI ; 1VGH ; 1VPF ; 1VPP ; 2FJG ; 2FJH ; 2QR0 ; 2VGH ; 2VPF ; 3BDY ; 3P9W ; 3QTK ; 3S1B ; 3S1K ; 3V2A ; 4DEQ ; 4GLN ; 4GLS ; 4KZN ; 4QAF ; 4WPB ; 4ZFF ; 5DN2 ; 5FV1 ; 5FV2 ; 5HHC ; 5HHD ; 5O4E ; 5T89 ; 6BFT ; 6D3O ; 6T9D ; 6V7K ; 6Z13 ; 6Z3F ; 6ZBR ; 6ZCD ; 6ZFL ; 7KEZ ; 7KF0 ; 7KF1 ; 7LL8 ; 7LL9
• Pfam ID: PF00341 ; PF14554
• Sequence:
  MTDRQTDTAPSPSYHLLPGRRRTVDAAASRGQGPEPAPGGGVEGVGARGVALKLFVQLLG
  CSRFGGAVVRAGEAEPSGAARSASSGREEPQPEEGEEEEEKEEERGPQWRLGARKPGSWT
  GEAAVCADSAPAARAPQALARASGRGGRVARRGAEESGPPHSPSRRGSASRAGPGRASET
  MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
  IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
  SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVPCGPCSERRKHLFVQ
  DPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
• Function: [N-VEGF]: Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A. Involved in protecting cells from hypoxia-mediated cell death; [VEGFA]: Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. Binds to the NRP1/neuropilin-1 receptor. Binding to NRP1 initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development. Also binds the DEAR/FBXW7-AS1 receptor ; [Isoform VEGF165B]: Binds to the KDR receptor but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.
• Tissue Specificity: Higher expression in pituitary tumors than the pituitary gland.; [Isoform VEGF189]: Widely expressed.; [Isoform VEGF165]: Widely expressed.; [Isoform VEGF121]: Widely expressed.; [Isoform VEGF206]: Not widely expressed.; [Isoform VEGF145]: Not widely expressed.
• 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)
  HIF-1 sig.ling pathway (hsa04066)
  PI3K-Akt sig.ling pathway (hsa04151)
  VEGF sig.ling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Bladder cancer (hsa05219)
  Rheumatoid arthritis (hsa05323)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  (Name not found)
  Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158)
  Signaling by VEGF (R-HSA-194138)
  VEGF ligand-receptor interactions (R-HSA-194313)
  VEGF binds to VEGFR leading to receptor dimerization (R-HSA-195399)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Vascular endothelial growth factor A, long form decreases the response to substance of Etoposide.	[80]
Warfarin	DMJYCVW	Approved	Vascular endothelial growth factor A, long form affects the response to substance of Warfarin.	[81]
Dobutamine	DMD1B8Z	Approved	Vascular endothelial growth factor A, long form affects the response to substance of Dobutamine.	[82]
Citrate	DM37NYK	Preclinical	Vascular endothelial growth factor A, long form affects the binding of Citrate.	[83]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Vascular endothelial growth factor A, long form affects the abundance of Uric acid.	[84]
Cyclic guanosine monophosphate	DMOU93V	Investigative	Vascular endothelial growth factor A, long form increases the abundance of Cyclic guanosine monophosphate.	[85]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Vascular endothelial growth factor A, long form.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Vascular endothelial growth factor A, long form.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Vascular endothelial growth factor A, long form.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vascular endothelial growth factor A, long form.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vascular endothelial growth factor A, long form.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Vascular endothelial growth factor A, long form.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Vascular endothelial growth factor A, long form.	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Vascular endothelial growth factor A, long form.	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Vascular endothelial growth factor A, long form.	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Vascular endothelial growth factor A, long form.	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Vascular endothelial growth factor A, long form.	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Vascular endothelial growth factor A, long form.	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Vascular endothelial growth factor A, long form.	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Vascular endothelial growth factor A, long form.	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Vascular endothelial growth factor A, long form.	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Vascular endothelial growth factor A, long form.	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Vascular endothelial growth factor A, long form.	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Vascular endothelial growth factor A, long form.	[17]
Marinol	DM70IK5	Approved	Marinol increases the expression of Vascular endothelial growth factor A, long form.	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Vascular endothelial growth factor A, long form.	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Vascular endothelial growth factor A, long form.	[21]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Vascular endothelial growth factor A, long form.	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Vascular endothelial growth factor A, long form.	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Vascular endothelial growth factor A, long form.	[24]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Vascular endothelial growth factor A, long form.	[25]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Vascular endothelial growth factor A, long form.	[26]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Vascular endothelial growth factor A, long form.	[27]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Vascular endothelial growth factor A, long form.	[28]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Vascular endothelial growth factor A, long form.	[29]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Vascular endothelial growth factor A, long form.	[30]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Vascular endothelial growth factor A, long form.	[31]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Vascular endothelial growth factor A, long form.	[32]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Vascular endothelial growth factor A, long form.	[33]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Vascular endothelial growth factor A, long form.	[34]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Vascular endothelial growth factor A, long form.	[16]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Vascular endothelial growth factor A, long form.	[35]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Vascular endothelial growth factor A, long form.	[36]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Vascular endothelial growth factor A, long form.	[37]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Vascular endothelial growth factor A, long form.	[38]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Vascular endothelial growth factor A, long form.	[39]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of Vascular endothelial growth factor A, long form.	[40]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Vascular endothelial growth factor A, long form.	[41]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Vascular endothelial growth factor A, long form.	[42]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Vascular endothelial growth factor A, long form.	[43]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Vascular endothelial growth factor A, long form.	[44]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Vascular endothelial growth factor A, long form.	[30]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Vascular endothelial growth factor A, long form.	[47]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Vascular endothelial growth factor A, long form.	[48]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Vascular endothelial growth factor A, long form.	[49]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Vascular endothelial growth factor A, long form.	[48]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Vascular endothelial growth factor A, long form.	[42]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Vascular endothelial growth factor A, long form.	[50]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Vascular endothelial growth factor A, long form.	[51]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Vascular endothelial growth factor A, long form.	[53]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Vascular endothelial growth factor A, long form.	[55]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Vascular endothelial growth factor A, long form.	[56]
Tofacitinib	DMBS370	Approved	Tofacitinib increases the expression of Vascular endothelial growth factor A, long form.	[57]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Vascular endothelial growth factor A, long form.	[46]
Romidepsin	DMT5GNL	Approved	Romidepsin decreases the expression of Vascular endothelial growth factor A, long form.	[58]
Nevirapine	DM6HX9B	Approved	Nevirapine decreases the expression of Vascular endothelial growth factor A, long form.	[59]
Propranolol	DM79NTF	Approved	Propranolol decreases the expression of Vascular endothelial growth factor A, long form.	[61]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Vascular endothelial growth factor A, long form.	[62]
Budesonide	DMJIBAW	Approved	Budesonide decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Ropivacaine	DMSPJG2	Approved	Ropivacaine decreases the expression of Vascular endothelial growth factor A, long form.	[64]
Fludarabine	DMVRLT7	Approved	Fludarabine decreases the expression of Vascular endothelial growth factor A, long form.	[65]
Cetrorelix	DMFD9Q6	Approved	Cetrorelix decreases the expression of Vascular endothelial growth factor A, long form.	[66]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of Vascular endothelial growth factor A, long form.	[67]
Emetine	DMCT2YF	Approved	Emetine decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Metoprolol	DMOJ0V6	Approved	Metoprolol decreases the expression of Vascular endothelial growth factor A, long form.	[61]
Digoxin	DMQCTIH	Approved	Digoxin decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Amiloride	DMRTSGP	Approved	Amiloride decreases the expression of Vascular endothelial growth factor A, long form.	[68]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the expression of Vascular endothelial growth factor A, long form.	[69]
Regorafenib	DMHSY1I	Approved	Regorafenib decreases the expression of Vascular endothelial growth factor A, long form.	[70]
Dacarbazine	DMNPZL4	Approved	Dacarbazine increases the expression of Vascular endothelial growth factor A, long form.	[71]
Romiplostim	DM3U7SZ	Approved	Romiplostim decreases the expression of Vascular endothelial growth factor A, long form.	[72]
Candesartan	DMRK8OT	Approved	Candesartan decreases the expression of Vascular endothelial growth factor A, long form.	[73]
Norethindrone	DMTY169	Approved	Norethindrone increases the expression of Vascular endothelial growth factor A, long form.	[74]
Albendazole	DMYZ57N	Approved	Albendazole increases the expression of Vascular endothelial growth factor A, long form.	[46]
Levonorgestrel	DM1DP7T	Approved	Levonorgestrel increases the expression of Vascular endothelial growth factor A, long form.	[74]
Betamethasone	DMAHJEF	Approved	Betamethasone decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Oxytetracycline	DMOVH1M	Approved	Oxytetracycline decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Triamcinolone	DM98IXF	Approved	Triamcinolone decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Meclocycline	DMSFQ8I	Approved	Meclocycline decreases the expression of Vascular endothelial growth factor A, long form.	[46]
Quinolones	DM5GVHU	Approved	Quinolones increases the expression of Vascular endothelial growth factor A, long form.	[76]
Fedratinib	DM4ZBK6	Approved	Fedratinib increases the expression of Vascular endothelial growth factor A, long form.	[57]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Vascular endothelial growth factor A, long form.	[77]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Vascular endothelial growth factor A, long form.	[78]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of Vascular endothelial growth factor A, long form.	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Vascular endothelial growth factor A, long form.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the secretion of Vascular endothelial growth factor A, long form.	[45]
Imatinib	DM7RJXL	Approved	Imatinib decreases the secretion of Vascular endothelial growth factor A, long form.	[52]
Ardeparin	DMYRX8B	Approved	Ardeparin affects the binding of Vascular endothelial growth factor A, long form.	[54]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the secretion of Vascular endothelial growth factor A, long form.	[60]
Epanova	DMHEAGL	Approved	Epanova decreases the secretion of Vascular endothelial growth factor A, long form.	[63]
Dipyridamole	DMXY30O	Approved	Dipyridamole increases the secretion of Vascular endothelial growth factor A, long form.	[56]
Valdecoxib	DMAY7H4	Approved	Valdecoxib increases the secretion of Vascular endothelial growth factor A, long form.	[75]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the secretion of Vascular endothelial growth factor A, long form.	[79]

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