Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ1ZMHK)

• DOT Name: Vascular endothelial growth factor C
• Synonyms: VEGF-C; Flt4 ligand; Flt4-L; Vascular endothelial growth factor-related protein; VRP
• Gene Name: VEGFC
• Related Disease:
  Lymphatic malformation 4
  Lymphatic malformation
• UniProt ID: VEGFC_HUMAN
• PDB ID: 2X1W; 2X1X; 4BSK; 6TJT
• Pfam ID: PF03128 ; PF00341
• Sequence:
  MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPDAGEATAYASKDLEEQL
  RSVSSVDELMTVLYPEYWKMYKCQLRKGGWQHNREQANLNSRTEETIKFAAAHYNTEILK
  SIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQCMNTSTSY
  LSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHSIIRRSLPATLPQCQAAN
  KTCPTNYMWNNHICRCLAQEDFMFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLR
  PASCGPHKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPRNQPLNPGKCAC
  ECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQKACEPGFSYSEEVCRCVPSYWKRPQMS
• Function: Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.
• Tissue Specificity: Expressed in the spleen . Expressed in the lymph node, thymus, appendix and bone marrow . Expressed in the heart, placenta, skeletal muscle, ovary and small intestine . Expressed in the prostate, testis and colon .
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  TNF sig.ling pathway (hsa04668)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  VEGF ligand-receptor interactions (R-HSA-194313)
  VEGF binds to VEGFR leading to receptor dimerization (R-HSA-195399)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphatic malformation 4	DIS73V0V	Strong	Autosomal dominant	[1]
Lymphatic malformation	DIS4D8VL	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Vascular endothelial growth factor C decreases the response to substance of Cytarabine.	[29]
Etoposide	DMNH3PG	Approved	Vascular endothelial growth factor C decreases the response to substance of Etoposide.	[29]
Vinblastine	DM5TVS3	Approved	Vascular endothelial growth factor C affects the response to substance of Vinblastine.	[30]

32 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 C.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vascular endothelial growth factor C.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vascular endothelial growth factor C.	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Vascular endothelial growth factor C.	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Vascular endothelial growth factor C.	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Vascular endothelial growth factor C.	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Vascular endothelial growth factor C.	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Vascular endothelial growth factor C.	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Vascular endothelial growth factor C.	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Vascular endothelial growth factor C.	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Vascular endothelial growth factor C.	[12]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Vascular endothelial growth factor C.	[13]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Vascular endothelial growth factor C.	[4]
Thalidomide	DM70BU5	Approved	Thalidomide affects the expression of Vascular endothelial growth factor C.	[14]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Vascular endothelial growth factor C.	[15]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of Vascular endothelial growth factor C.	[16]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Vascular endothelial growth factor C.	[17]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Vascular endothelial growth factor C.	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Vascular endothelial growth factor C.	[19]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Vascular endothelial growth factor C.	[12]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Vascular endothelial growth factor C.	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Vascular endothelial growth factor C.	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vascular endothelial growth factor C.	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Vascular endothelial growth factor C.	[23]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Vascular endothelial growth factor C.	[24]
Nimesulide	DMR1NMD	Terminated	Nimesulide decreases the expression of Vascular endothelial growth factor C.	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Vascular endothelial growth factor C.	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Vascular endothelial growth factor C.	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Vascular endothelial growth factor C.	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Vascular endothelial growth factor C.	[27]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Vascular endothelial growth factor C.	[28]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Vascular endothelial growth factor C.	[4]

References

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