Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJKE6VW)

• DOT Name: Phosphatidylinositol-glycan biosynthesis class F protein (PIGF)
• Synonyms: PIG-F; GPI11 homolog
• Gene Name: PIGF
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Fetal growth restriction
  Germ cell tumor
  Hemangioma
  Neoplasm
  Paroxysmal nocturnal haemoglobinuria
  Retinoblastoma
  Systemic lupus erythematosus
  Colorectal carcinoma
  Bone osteosarcoma
  Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
  Osteosarcoma
• UniProt ID: PIGF_HUMAN
• Pfam ID: PF06699
• Sequence:
  MKDNDIKRLLYTHLLCIFSIILSVFIPSLFLENFSILETHLTWLCICSGFVTAVNLVLYL
  VVKPNTSSKRSSLSHKVTGFLKCCIYFLMSCFSFHVIFVLYGAPLIELALETFLFAVILS
  TFTTVPCLCLLGPNLKAWLRVFSRNGVTSIWENSLQITTISSFVGAWLGALPIPLDWERP
  WQVWPISCTLGATFGYVAGLVISPLWIYWNRKQLTYKNN
• Function: Involved in GPI-anchor biosynthesis. It acts through the transfer of ethanolamine phosphate to the third mannose of GPI.
• KEGG Pathway:
  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (hsa00563)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of glycosylphosphatidylinositol (GPI) (R-HSA-162710)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Fetal growth restriction	DIS5WEJ5	Strong	Genetic Variation	[2]
Germ cell tumor	DIS62070	Strong	Altered Expression	[3]
Hemangioma	DISDCGAG	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Biomarker	[6]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[9]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[10]
Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome	DIS5ELJX	Limited	Autosomal recessive	[11]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[12]

7 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 Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[17]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[18]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phosphatidylinositol-glycan biosynthesis class F protein (PIGF).	[19]

References

• [1] Placenta growth factor and sFlt-1 as biomarkers in ischemic heart disease and heart failure: a review.Biomark Med. 2019 Jun;13(9):785-799. doi: 10.2217/bmm-2018-0492. Epub 2019 Jun 3.
• [2] Better prediction for FGR (fetal growth restriction) with the sFlt-1/PIGF ratio: A case-control study.Medicine (Baltimore). 2019 Jun;98(26):e16069. doi: 10.1097/MD.0000000000016069.
• [3] Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the placenta-derived growth factor.Oncogene. 1996 Aug 1;13(3):577-87.
• [4] Serum cytokine profiles are altered in patients with progressive infantile hemangioma.Biosci Trends. 2018 Sep 19;12(4):438-441. doi: 10.5582/bst.2018.01118. Epub 2018 Aug 26.
• [5] Molecular insight of regorafenib treatment for colorectal cancer.Cancer Treat Rev. 2019 Dec;81:101912. doi: 10.1016/j.ctrv.2019.101912. Epub 2019 Oct 28.
• [6] Structure and chromosomal localization of the GPI-anchor synthesis gene PIGF and its pseudogene psi PIGF.Genomics. 1995 Oct 10;29(3):804-7. doi: 10.1006/geno.1995.9929.
• [7] Correlations between claudin-1 and PIGF expressions in retinoblastoma.Eur Rev Med Pharmacol Sci. 2018 Jul;22(13):4196-4203. doi: 10.26355/eurrev_201807_15413.
• [8] Circulating proangiogenic molecules PIGF, SDF-1 and sVCAM-1 in patients with systemic lupus erythematosus.Eur Cytokine Netw. 2007 Dec;18(4):181-7. doi: 10.1684/ecn.2007.0103. Epub 2007 Oct 26.
• [9] The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls.Expert Opin Biol Ther. 2020 Jan;20(1):15-22. doi: 10.1080/14712598.2020.1677603. Epub 2019 Oct 16.
• [10] Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome.Oncol Lett. 2018 Oct;16(4):4953-4960. doi: 10.3892/ol.2018.9239. Epub 2018 Jul 31.
• [11] PIGF deficiency causes a phenotype overlapping with DOORS syndrome. Hum Genet. 2021 Jun;140(6):879-884. doi: 10.1007/s00439-020-02251-2. Epub 2021 Jan 2.
• [12] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [17] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [18] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [19] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.