Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVIX6J0)

• DOT Name: Fibroblast growth factor 22 (FGF22)
• Synonyms: FGF-22
• Gene Name: FGF22
• Related Disease:
  Depression
  Lung adenocarcinoma
  Staphylococcus aureus infection
  Systemic lupus erythematosus
• UniProt ID: FGF22_HUMAN
• Pfam ID: PF00167
• Sequence:
  MRRRLWLGLAWLLLARAPDAAGTPSASRGPRSYPHLEGDVRWRRLFSSTHFFLRVDPGGR
  VQGTRWRHGQDSILEIRSVHVGVVVIKAVSSGFYVAMNRRGRLYGSRLYTVDCRFRERIE
  ENGHNTYASQRWRRRGQPMFLALDRRGGPRPGGRTRRYHLSAHFLPVLVS
• Function: Plays a role in the fasting response, glucose homeostasis, lipolysis and lipogenesis. Can stimulate cell proliferation (in vitro). May be involved in hair development.
• 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)
  PIP3 activates AKT signaling (R-HSA-1257604)
  FGFR1b ligand binding and activation (R-HSA-190370)
  FGFR2b ligand binding and activation (R-HSA-190377)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Phospholipase C-mediated cascade (R-HSA-5654219)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  Downstream signaling of activated FGFR1 (R-HSA-5654687)
  SHC-mediated cascade (R-HSA-5654688)
  PI-3K cascade (R-HSA-5654689)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Staphylococcus aureus infection	DISK6PTH	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]

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 Fibroblast growth factor 22 (FGF22).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fibroblast growth factor 22 (FGF22).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Fibroblast growth factor 22 (FGF22).	[5]
Letrozole	DMH07Y3	Approved	Letrozole increases the expression of Fibroblast growth factor 22 (FGF22).	[6]

References

• [1] Fibroblast growth factor 22 is a novel modulator of depression through interleukin-1.CNS Neurosci Ther. 2017 Nov;23(11):907-916. doi: 10.1111/cns.12760. Epub 2017 Sep 25.
• [2] Integrated Analysis of Transcriptome and Prognosis Data Identifies FGF22 as a Prognostic Marker of Lung Adenocarcinoma.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819827317. doi: 10.1177/1533033819827317.
• [3] An OMICS-based study of the role of C3dg in keratinocytes: RNA sequencing, antibody-chip array, and bioinformatics approaches.Int J Biol Macromol. 2019 Jul 15;133:391-411. doi: 10.1016/j.ijbiomac.2019.04.039. Epub 2019 Apr 8.
• [4] 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.
• [5] 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.
• [6] Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome. Fertil Steril. 2011 Oct;96(4):1051-6. doi: 10.1016/j.fertnstert.2011.07.1092.
• [7] 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.