Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWM1KCM)

• DOT Name: Fibroblast growth factor-binding protein 3 (FGFBP3)
• Synonyms: FGF-BP3; FGF-binding protein 3; FGFBP-3
• Gene Name: FGFBP3
• Related Disease:
  Hyperglycemia
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Anxiety
  Anxiety disorder
• UniProt ID: FGFP3_HUMAN
• Pfam ID: PF06473
• Sequence:
  MTPPKLRASLSPSLLLLLSGCLLAAARREKGAASNVAEPVPGPTGGSSGRFLSPEQHACS
  WQLLLPAPEAAAGSELALRCQSPDGARHQCAYRGHPERCAAYAARRAHFWKQVLGGLRKK
  RRPCHDPAPLQARLCAGKKGHGAELRLVPRASPPARPTVAGFAGESKPRARNRGRTRERA
  SGPAAGTPPPQSAPPKENPSERKTNEGKRKAALVPNEERPMGTGPDPDGLDGNAELTETY
  CAEKWHSLCNFFVNFWNG
• Function: Heparin-binding protein which binds to FGF2, prevents binding of FGF2 to heparin and probably inhibits immobilization of FGF2 on extracellular matrix glycosaminoglycans, allowing its release and subsequent activation of FGFR signaling which leads to increased vascular permeability.
• Reactome Pathway: FGFR2b ligand binding and activation (R-HSA-190377)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Limited	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[2]

11 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 Fibroblast growth factor-binding protein 3 (FGFBP3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fibroblast growth factor-binding protein 3 (FGFBP3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fibroblast growth factor-binding protein 3 (FGFBP3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fibroblast growth factor-binding protein 3 (FGFBP3).	[13]

References

• [1] Fibroblast Growth Factor Binding Protein 3 (FGFBP3) impacts carbohydrate and lipid metabolism.Sci Rep. 2018 Oct 29;8(1):15973. doi: 10.1038/s41598-018-34238-5.
• [2] Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors.Mol Cell Neurosci. 2011 Jan;46(1):200-12. doi: 10.1016/j.mcn.2010.09.003. Epub 2010 Sep 21.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.