Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6513W2)

• DOT Name: Fibroblast growth factor 11 (FGF11)
• Synonyms: FGF-11; Fibroblast growth factor homologous factor 3; FHF-3
• Gene Name: FGF11
• Related Disease:
  Bone giant cell tumor
  Diabetic kidney disease
  Hyperinsulinemia
  Non-insulin dependent diabetes
  Brugada syndrome
  Nasopharyngeal carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: FGF11_HUMAN
• Pfam ID: PF00167
• Sequence:
  MAALASSLIRQKREVREPGGSRPVSAQRRVCPRGTKSLCQKQLLILLSKVRLCGGRPARP
  DRGPEPQLKGIVTKLFCRQGFYLQANPDGSIQGTPEDTSSFTHFNLIPVGLRVVTIQSAK
  LGHYMAMNAEGLLYSSPHFTAECRFKECVFENYYVLYASALYRQRRSGRAWYLGLDKEGQ
  VMKGNRVKKTKAAAHFLPKLLEVAMYQEPSLHSVPEASPSSPPAP
• Function: Probably involved in nervous system development and function.
• Tissue Specificity: Nervous system.
• Reactome Pathway: Phase 0 - rapid depolarisation (R-HSA-5576892)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone giant cell tumor	DIS0RGK9	Strong	Altered Expression	[1]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[2]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[3]
Brugada syndrome	DISSGN0E	Limited	Biomarker	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]
Prostate cancer	DISF190Y	Limited	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibroblast growth factor 11 (FGF11).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Fibroblast growth factor 11 (FGF11).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fibroblast growth factor 11 (FGF11).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Fibroblast growth factor 11 (FGF11).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fibroblast growth factor 11 (FGF11).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibroblast growth factor 11 (FGF11).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fibroblast growth factor 11 (FGF11).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fibroblast growth factor 11 (FGF11).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Fibroblast growth factor 11 (FGF11).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fibroblast growth factor 11 (FGF11).	[13]

References

• [1] Hypoxia-Induced Fibroblast Growth Factor 11 Stimulates Osteoclast-Mediated Resorption of Bone.Calcif Tissue Int. 2017 Apr;100(4):382-391. doi: 10.1007/s00223-016-0228-1. Epub 2017 Jan 18.
• [2] Circ_0080425 inhibits cell proliferation and fibrosis in diabetic nephropathy via sponging miR-24-3p and targeting fibroblast growth factor 11.J Cell Physiol. 2020 May;235(5):4520-4529. doi: 10.1002/jcp.29329. Epub 2019 Nov 3.
• [3] T2DM inhibition of endothelial miR-342-3p facilitates angiogenic dysfunction via repression of FGF11 signaling.Biochem Biophys Res Commun. 2018 Sep 3;503(1):71-78. doi: 10.1016/j.bbrc.2018.05.179. Epub 2018 Jun 7.
• [4] FGF12 is a candidate Brugada syndrome locus.Heart Rhythm. 2013 Dec;10(12):1886-94. doi: 10.1016/j.hrthm.2013.09.064. Epub 2013 Oct 4.
• [5] Exosomal miR-24-3p impedes T-cell function by targeting FGF11 and serves as a potential prognostic biomarker for nasopharyngeal carcinoma.J Pathol. 2016 Nov;240(3):329-340. doi: 10.1002/path.4781.
• [6] Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11miRNA-541androgen receptor (AR)MMP9 signaling.Mol Oncol. 2015 Jan;9(1):44-57. doi: 10.1016/j.molonc.2014.07.013. Epub 2014 Jul 29.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [9] 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.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.