Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2SKDGM)

• DOT Name: Fibroblast growth factor 9 (FGF9)
• Synonyms: FGF-9; Glia-activating factor; GAF; Heparin-binding growth factor 9; HBGF-9
• Gene Name: FGF9
• Related Disease:
  Lung cancer
  Lung neoplasm
  Meningioma
  Rheumatoid arthritis
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Cerebellar ataxia
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Glioblastoma multiforme
  Isolated cleft lip
  Isolated cleft palate
  Lung adenocarcinoma
  Lung carcinoma
  Major depressive disorder
  Malignant mesothelioma
  Multiple synostoses syndrome 1
  Multiple synostoses syndrome 3
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Pleuropulmonary blastoma
  Schizophrenia
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Craniosynostosis
  Hepatocellular carcinoma
  Psychotic disorder
  Multiple synostoses syndrome
  Glioma
  Huntington disease
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: FGF9_HUMAN
• PDB ID: 1G82; 1IHK; 5W59
• Pfam ID: PF00167
• Sequence:
  MAPLGEVGNYFGVQDAVPFGNVPVLPVDSPVLLSDHLGQSEAGGLPRGPAVTDLDHLKGI
  LRRRQLYCRTGFHLEIFPNGTIQGTRKDHSRFGILEFISIAVGLVSIRGVDSGLYLGMNE
  KGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKR
  HQKFTHFLPRPVDPDKVPELYKDILSQS
• Function: Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors.
• Tissue Specificity: Glial cells.
• 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 FGFR1 (R-HSA-1839122)
  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)
  FGFR1c ligand binding and activation (R-HSA-190373)
  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-5654219)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  Phospholipase C-mediated cascade (R-HSA-5654227)
  Phospholipase C-mediated cascade (R-HSA-5654228)
  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)
  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 FGFR1 signaling (R-HSA-5654726)
  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 FGFR1 in disease (R-HSA-5655302)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Transcriptional regulation of testis differentiation (R-HSA-9690406)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[1]
Meningioma	DISPT4TG	Definitive	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Isolated cleft lip	DIS2O2JV	Strong	Biomarker	[12]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[13]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[14]
Multiple synostoses syndrome 1	DISD179V	Strong	Biomarker	[15]
Multiple synostoses syndrome 3	DIS6RWVX	Strong	Autosomal dominant	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Parkinson disease	DISQVHKL	Strong	Biomarker	[7]
Pleuropulmonary blastoma	DIS3UCS9	Strong	Biomarker	[18]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[20]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[20]
Craniosynostosis	DIS6J405	moderate	Genetic Variation	[21]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[22]
Psychotic disorder	DIS4UQOT	moderate	Altered Expression	[23]
Multiple synostoses syndrome	DISGA3UA	Supportive	Autosomal dominant	[16]
Glioma	DIS5RPEH	Limited	Biomarker	[24]
Huntington disease	DISQPLA4	Limited	Biomarker	[25]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[26]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[28]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[6]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Fibroblast growth factor 9 (FGF9) affects the response to substance of Cisplatin.	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fibroblast growth factor 9 (FGF9).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fibroblast growth factor 9 (FGF9).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibroblast growth factor 9 (FGF9).	[31]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fibroblast growth factor 9 (FGF9).	[33]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fibroblast growth factor 9 (FGF9).	[34]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Fibroblast growth factor 9 (FGF9).	[35]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Fibroblast growth factor 9 (FGF9).	[33]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Fibroblast growth factor 9 (FGF9).	[36]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Fibroblast growth factor 9 (FGF9).	[37]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Fibroblast growth factor 9 (FGF9).	[38]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Fibroblast growth factor 9 (FGF9).	[39]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Fibroblast growth factor 9 (FGF9).	[33]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Fibroblast growth factor 9 (FGF9).	[33]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Fibroblast growth factor 9 (FGF9).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fibroblast growth factor 9 (FGF9).	[42]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Fibroblast growth factor 9 (FGF9).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Fibroblast growth factor 9 (FGF9).	[45]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Fibroblast growth factor 9 (FGF9).	[46]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid increases the expression of Fibroblast growth factor 9 (FGF9).	[47]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Investigative	ISOPENTENYL PYROPHOSPHATE increases the expression of Fibroblast growth factor 9 (FGF9).	[48]

3 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 9 (FGF9).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fibroblast growth factor 9 (FGF9).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fibroblast growth factor 9 (FGF9).	[44]

References

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