Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP4BSCH)

• DOT Name: Fibroblast growth factor-binding protein 1 (FGFBP1)
• Synonyms: FGF-BP; FGF-BP1; FGF-binding protein 1; FGFBP-1; 17 kDa heparin-binding growth factor-binding protein; 17 kDa HBGF-binding protein; HBp17
• Gene Name: FGFBP1
• UniProt ID: FGFP1_HUMAN
• Pfam ID: PF06473
• Sequence:
  MKICSLTLLSFLLLAAQVLLVEGKKKVKNGLHSKVVSEQKDTLGNTQIKQKSRPGNKGKF
  VTKDQANCRWAATEQEEGISLKVECTQLDHEFSCVFAGNPTSCLKLKDERVYWKQVARNL
  RSQKDICRYSKTAVKTRVCRKDFPESSLKLVSSTLFGNTKPRKEKTEMSPREHIKGKETT
  PSSLAVTQTMATKAPECVEDPDMANQRKTALEFCGETWSSLCTFFLSIVQDTSC
• Function: Acts as a carrier protein that release fibroblast-binding factors (FGFs) from the extracellular matrix (EM) storage and thus enhance the mitogenic activity of FGFs. Enhances FGF2 signaling during tissue repair, angiogenesis and in tumor growth.
• Tissue Specificity: Expressed in the suprabasal region of the epidermis, in hair follicles, the basement membrane at the dermo-epidermal junction (occasionally extending into the basement membrane of dermal blood vessels), wounded skin and several invasive squamous cell carcinomas (at protein level). Expressed in normal and wounded skin and various squamous cell carcinomas.
• Reactome Pathway: FGFR2b ligand binding and activation (R-HSA-190377)

Molecular Interaction Atlas (MIA) of This DOT

13 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 Fibroblast growth factor-binding protein 1 (FGFBP1).	[1]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[7]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[8]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fibroblast growth factor-binding protein 1 (FGFBP1).	[15]

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 1 (FGFBP1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fibroblast growth factor-binding protein 1 (FGFBP1).	[10]

References

• [1] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [2] 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.
• [3] 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.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115100. doi: 10.1016/j.taap.2020.115100. Epub 2020 Jun 6.
• [9] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.