Details of Drug Off-Target (DOT)

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

• DOT Name: Fibroblast growth factor 5 (FGF5)
• Synonyms: FGF-5; Heparin-binding growth factor 5; HBGF-5; Smag-82
• Gene Name: FGF5
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Baldness, male pattern
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Esophageal squamous cell carcinoma
  Essential hypertension
  Fatty liver disease
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Renal cell carcinoma
  Retinitis pigmentosa
  Atrial fibrillation
  Familial atrial fibrillation
  Familial isolated trichomegaly
  Acquired immune deficiency syndrome
  Alopecia
  Androgenetic alopecia
  Chronic pancreatitis
  HER2/NEU overexpressing breast cancer
  Hereditary hemochromatosis
  Kaposi sarcoma
  Melanoma
  Osteoarthritis
  Trichomegaly
• UniProt ID: FGF5_HUMAN
• Pfam ID: PF00167
• Sequence:
  MSLSFLLLLFFSHLILSAWAHGEKRLAPKGQPGPAATDRNPRGSSSRQSSSSAMSSSSAS
  SSPAASLGSQGSGLEQSSFQWSPSGRRTGSLYCRVGIGFHLQIYPDGKVNGSHEANMLSV
  LEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQENSYNTYASAIHR
  TEKTGREWYVALNKRGKAKRGCSPRVKPQHISTHFLPRFKQSEQPELSFTVTVPEKKKPP
  SPIKPKIPLSAPRKNTNSVKYRLKFRFG
• Function: Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase.
• Tissue Specificity: Expressed in neonatal brain.
• 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)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Baldness, male pattern	DIS9C9RO	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[7]
Essential hypertension	DIS7WI98	Strong	Altered Expression	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[11]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[1]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[12]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[13]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[13]
Familial isolated trichomegaly	DISOVJZO	Supportive	Autosomal recessive	[14]
Acquired immune deficiency syndrome	DISL5UOX	Limited	Biomarker	[15]
Alopecia	DIS37HU4	Limited	Genetic Variation	[16]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[17]
Chronic pancreatitis	DISBUOMJ	Limited	Altered Expression	[18]
HER2/NEU overexpressing breast cancer	DISYKID5	Limited	Altered Expression	[6]
Hereditary hemochromatosis	DISVG5MT	Limited	Biomarker	[19]
Kaposi sarcoma	DISC1H1Z	Limited	Altered Expression	[15]
Melanoma	DIS1RRCY	Limited	Biomarker	[20]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[21]
Trichomegaly	DIS9JYMB	No Known	Autosomal recessive	[14]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Fibroblast growth factor 5 (FGF5) affects the response to substance of Doxorubicin.	[34]
Paclitaxel	DMLB81S	Approved	Fibroblast growth factor 5 (FGF5) affects the response to substance of Paclitaxel.	[34]
Warfarin	DMJYCVW	Approved	Fibroblast growth factor 5 (FGF5) affects the response to substance of Warfarin.	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Fibroblast growth factor 5 (FGF5).	[22]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Fibroblast growth factor 5 (FGF5).	[23]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Fibroblast growth factor 5 (FGF5).	[24]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Fibroblast growth factor 5 (FGF5).	[25]
Ardeparin	DMYRX8B	Approved	Ardeparin affects the activity of Fibroblast growth factor 5 (FGF5).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Fibroblast growth factor 5 (FGF5).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fibroblast growth factor 5 (FGF5).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fibroblast growth factor 5 (FGF5).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fibroblast growth factor 5 (FGF5).	[31]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Fibroblast growth factor 5 (FGF5).	[32]
Suramin	DMTOUY9	Investigative	Suramin increases the expression of Fibroblast growth factor 5 (FGF5).	[33]

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 5 (FGF5).	[28]

References

• [1] Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas.Cancer Res. 2001 Jul 15;61(14):5511-6.
• [2] Downregulation of fibroblast growth factor 5 inhibits cell growth and invasion of human nonsmall-cell lung cancer cells.J Cell Biochem. 2019 May;120(5):8238-8246. doi: 10.1002/jcb.28107. Epub 2018 Dec 5.
• [3] Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness.Nat Commun. 2017 Mar 8;8:14694. doi: 10.1038/ncomms14694.
• [4] FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway.Cancer Manag Res. 2019 Jul 10;11:6457-6466. doi: 10.2147/CMAR.S200234. eCollection 2019.
• [5] FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities.Oncogene. 2008 Jul 10;27(30):4180-90. doi: 10.1038/onc.2008.61. Epub 2008 Mar 24.
• [6] Tumor-Associated Fibroblasts Promote HER2-Targeted Therapy Resistance through FGFR2 Activation.Clin Cancer Res. 2020 Mar 15;26(6):1432-1448. doi: 10.1158/1078-0432.CCR-19-0353. Epub 2019 Nov 7.
• [7] FGF5 methylation is a sensitivity marker of esophageal squamous cell carcinoma to definitive chemoradiotherapy.Sci Rep. 2019 Sep 16;9(1):13347. doi: 10.1038/s41598-019-50005-6.
• [8] Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance.Saudi J Biol Sci. 2018 Mar;25(3):469-473. doi: 10.1016/j.sjbs.2017.11.043. Epub 2017 Nov 16.
• [9] Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice.Sci Rep. 2016 Oct 6;6:34466. doi: 10.1038/srep34466.
• [10] Exosomal miR-9-3p suppresses HBGF-5 expression and is a functional biomarker in hepatocellular carcinoma.Minerva Med. 2018 Feb;109(1):15-23. doi: 10.23736/S0026-4806.17.05167-9. Epub 2017 Jul 27.
• [11] Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population.Gene. 2018 Dec 30;679:320-327. doi: 10.1016/j.gene.2018.09.019. Epub 2018 Sep 12.
• [12] Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18.Mol Ther. 2001 Apr;3(4):507-15. doi: 10.1006/mthe.2001.0289.
• [13] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [14] FGF5 is a crucial regulator of hair length in humans. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10648-53. doi: 10.1073/pnas.1402862111. Epub 2014 Jul 2.
• [15] Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in situ hybridization.Am J Pathol. 1991 Jan;138(1):9-15.
• [16] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [17] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [18] Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements of the pancreas in chronic pancreatitis.Gut. 1998 Jul;43(1):134-9. doi: 10.1136/gut.43.1.134.
• [19] Hedgehog signaling is active in human prostate cancer stroma and regulates proliferation and differentiation of adjacent epithelium.Prostate. 2013 Dec;73(16):1810-23. doi: 10.1002/pros.22720. Epub 2013 Sep 16.
• [20] FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo.Oncotarget. 2017 Sep 23;8(50):87750-87762. doi: 10.18632/oncotarget.21184. eCollection 2017 Oct 20.
• [21] Fibroblast growth factor-5 promotes spermatogonial stem cell proliferation via ERK and AKT activation.Stem Cell Res Ther. 2019 Jan 22;10(1):40. doi: 10.1186/s13287-019-1139-7.
• [22] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [23] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [24] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [25] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [26] Activation of fibroblast growth factor (FGF) receptors by recombinant human FGF-5. Oncogene. 1993 May;8(5):1311-6.
• [27] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [28] 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.
• [29] 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.
• [30] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [31] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [32] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [33] Increased expression of fibroblast growth factors (FGFs) and their receptor by protamine and suramin on Kaposi's sarcoma-derived cells. Anticancer Res. 1993 Jul-Aug;13(4):887-90.
• [34] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [35] Influence of common and rare genetic variation on warfarin dose among African-Americans and European-Americans using the exome array. Pharmacogenomics. 2017 Jul;18(11):1059-1073. doi: 10.2217/pgs-2017-0046. Epub 2017 Jul 7.