Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI7131S)

• DOT Name: Acidic fibroblast growth factor intracellular-binding protein (FIBP)
• Synonyms: aFGF intracellular-binding protein; FGF-1 intracellular-binding protein
• Gene Name: FIBP
• Related Disease:
  Childhood kidney Wilms tumor
  Colorectal carcinoma
  Liver cirrhosis
  Overgrowth syndrome
  Renal dysplasia
  Tall stature-intellectual disability-renal anomalies syndrome
  Wilms tumor
  Ankylosing spondylitis
  Crohn disease
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: FIBP_HUMAN
• Pfam ID: PF05427
• Sequence:
  MTSELDIFVGNTTLIDEDVYRLWLDGYSVTDAVALRVRSGILEQTGATAAVLQSDTMDHY
  RTFHMLERLLHAPPKLLHQLIFQIPPSRQALLIERYYAFDEAFVREVLGKKLSKGTKKDL
  DDISTKTGITLKSCRRQFDNFKRVFKVVEEMRGSLVDNIQQHFLLSDRLARDYAAIVFFA
  NNRFETGKKKLQYLSFGDFAFCAELMIQNWTLGAVGEAPTDPDSQMDDMDMDLDKEFLQD
  LKELKVLVADKDLLDLHKSLVCTALRGKLGVFSEMEANFKNLSRGLVNVAAKLTHNKDVR
  DLFVDLVEKFVEPCRSDHWPLSDVRFFLNQYSASVHSLDGFRHQALWDRYMGTLRGCLLR
  LYHD
• Function: May be involved in mitogenic function of FGF1. May mediate with IER2 FGF-signaling in the establishment of laterality in the embryo.
• Tissue Specificity: Highly expressed in heart, skeletal muscle and pancreas. Expressed at lower levels in brain. Also found in placenta, liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[2]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[3]
Overgrowth syndrome	DISHK54G	Strong	Biomarker	[1]
Renal dysplasia	DIS3DFGD	Strong	Genetic Variation	[1]
Tall stature-intellectual disability-renal anomalies syndrome	DIS7XDNC	Strong	Autosomal recessive	[4]
Wilms tumor	DISB6T16	Strong	Biomarker	[1]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[5]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[5]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[5]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[5]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[5]

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 Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Acidic fibroblast growth factor intracellular-binding protein (FIBP).	[8]

References

• [1] A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene. Am J Med Genet A. 2016 Aug;170(8):2111-8. doi: 10.1002/ajmg.a.37741. Epub 2016 May 17.
• [2] FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer via regulating GSK3-related pathways.Oncogenesis. 2018 Oct 2;7(9):77. doi: 10.1038/s41389-018-0088-9.
• [3] Angiogenic factor expression in hepatic cirrhosis.Mediators Inflamm. 2007;2007:67187. doi: 10.1155/2007/67187. Epub 2007 Feb 28.
• [4] Homozygous FIBP nonsense variant responsible of syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities. Clin Genet. 2016 May;89(5):e1-4. doi: 10.1111/cge.12704. Epub 2016 Jan 20.
• [5] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [6] 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.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.