Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7KJF8)

• DOT Name: Fibroblast growth factor 18 (FGF18)
• Synonyms: FGF-18; zFGF5
• Gene Name: FGF18
• UniProt ID: FGF18_HUMAN
• PDB ID: 4CJM
• Pfam ID: PF00167
• Sequence:
  MYSAPSACTCLCLHFLLLCFQVQVLVAEENVDFRIHVENQTRARDDVSRKQLRLYQLYSR
  TSGKHIQVLGRRISARGEDGDKYAQLLVETDTFGSQVRIKGKETEFYLCMNRKGKLVGKP
  DGTSKECVFIEKVLENNYTALMSAKYSGWYVGFTKKGRPRKGPKTRENQQDVHFMKRYPK
  GQPELQKPFKYTTVTKRSRRIRPTHPA
• Function: Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  (FGFR2)
  (FGFR3)
  (FGFR4)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Signaling by activated point mutants of FGFR3 (R-HSA-1839130)
  FGFR4 ligand binding and activation (R-HSA-190322)
  FGFR3b ligand binding and activation (R-HSA-190371)
  FGFR3c ligand binding and activation (R-HSA-190372)
  FGFR2c ligand binding and activation (R-HSA-190375)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  Phospholipase C-mediated cascade (R-HSA-5654227)
  Phospholipase C-mediated cascade (R-HSA-5654228)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  SHC-mediated cascade (R-HSA-5654704)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  PI-3K cascade (R-HSA-5654710)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  PI-3K cascade (R-HSA-5654720)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  FGFRL1 modulation of FGFR1 signaling (R-HSA-5658623)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Fibroblast growth factor 18 (FGF18).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibroblast growth factor 18 (FGF18).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fibroblast growth factor 18 (FGF18).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fibroblast growth factor 18 (FGF18).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Fibroblast growth factor 18 (FGF18).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fibroblast growth factor 18 (FGF18).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibroblast growth factor 18 (FGF18).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Fibroblast growth factor 18 (FGF18).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fibroblast growth factor 18 (FGF18).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fibroblast growth factor 18 (FGF18).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fibroblast growth factor 18 (FGF18).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Fibroblast growth factor 18 (FGF18).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Fibroblast growth factor 18 (FGF18).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibroblast growth factor 18 (FGF18).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Fibroblast growth factor 18 (FGF18).	[16]
Taxifolin	DMQJSF9	Preclinical	Taxifolin decreases the expression of Fibroblast growth factor 18 (FGF18).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Fibroblast growth factor 18 (FGF18).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fibroblast growth factor 18 (FGF18).	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Fibroblast growth factor 18 (FGF18).	[20]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone affects the expression of Fibroblast growth factor 18 (FGF18).	[21]

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 18 (FGF18).	[15]

References

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• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] The chemopreventive effect of taxifolin is exerted through ARE-dependent gene regulation. Biol Pharm Bull. 2007 Jun;30(6):1074-9.
• [18] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [19] 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.
• [20] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [21] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.