Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB5ZN4Q)

• DOT Name: Fibronectin (FN1)
• Synonyms: FN; Cold-insoluble globulin; CIG
• Gene Name: FN1
• Related Disease:
  Spondylometaphyseal dysplasia, 'corner fracture' type
  Glomerulopathy with fibronectin deposits 2
  Fibronectin glomerulopathy
• UniProt ID: FINC_HUMAN
• PDB ID: 1E88 ; 1E8B ; 1FBR ; 1FNA ; 1FNF ; 1FNH ; 1J8K ; 1O9A ; 1OWW ; 1Q38 ; 1QGB ; 1QO6 ; 1TTF ; 1TTG ; 2CG6 ; 2CG7 ; 2CK2 ; 2CKU ; 2EC3 ; 2FN2 ; 2FNB ; 2GEE ; 2H41 ; 2H45 ; 2HA1 ; 2MNU ; 2N1K ; 2OCF ; 2RKY ; 2RKZ ; 2RL0 ; 3CAL ; 3EJH ; 3GXE ; 3M7P ; 3MQL ; 3R8Q ; 3T1W ; 3ZRZ ; 4GH7 ; 4JE4 ; 4JEG ; 4LXO ; 4MMX ; 4MMY ; 4MMZ ; 4PZ5 ; 5DC0 ; 5DC4 ; 5DC9 ; 5DFT ; 5J6Z ; 5J7C ; 5M0A ; 5N47 ; 5N48 ; 6HNF ; 6MFA ; 6MSV ; 6NAJ ; 6XAX ; 6XAY ; 7NWL
• Pfam ID: PF00039 ; PF00040 ; PF00041
• Sequence:
  MLRGPGPGLLLLAVQCLGTAVPSTGASKSKRQAQQMVQPQSPVAVSQSKPGCYDNGKHYQ
  INQQWERTYLGNALVCTCYGGSRGFNCESKPEAEETCFDKYTGNTYRVGDTYERPKDSMI
  WDCTCIGAGRGRISCTIANRCHEGGQSYKIGDTWRRPHETGGYMLECVCLGNGKGEWTCK
  PIAEKCFDHAAGTSYVVGETWEKPYQGWMMVDCTCLGEGSGRITCTSRNRCNDQDTRTSY
  RIGDTWSKKDNRGNLLQCICTGNGRGEWKCERHTSVQTTSSGSGPFTDVRAAVYQPQPHP
  QPPPYGHCVTDSGVVYSVGMQWLKTQGNKQMLCTCLGNGVSCQETAVTQTYGGNSNGEPC
  VLPFTYNGRTFYSCTTEGRQDGHLWCSTTSNYEQDQKYSFCTDHTVLVQTRGGNSNGALC
  HFPFLYNNHNYTDCTSEGRRDNMKWCGTTQNYDADQKFGFCPMAAHEEICTTNEGVMYRI
  GDQWDKQHDMGHMMRCTCVGNGRGEWTCIAYSQLRDQCIVDDITYNVNDTFHKRHEEGHM
  LNCTCFGQGRGRWKCDPVDQCQDSETGTFYQIGDSWEKYVHGVRYQCYCYGRGIGEWHCQ
  PLQTYPSSSGPVEVFITETPSQPNSHPIQWNAPQPSHISKYILRWRPKNSVGRWKEATIP
  GHLNSYTIKGLKPGVVYEGQLISIQQYGHQEVTRFDFTTTSTSTPVTSNTVTGETTPFSP
  LVATSESVTEITASSFVVSWVSASDTVSGFRVEYELSEEGDEPQYLDLPSTATSVNIPDL
  LPGRKYIVNVYQISEDGEQSLILSTSQTTAPDAPPDTTVDQVDDTSIVVRWSRPQAPITG
  YRIVYSPSVEGSSTELNLPETANSVTLSDLQPGVQYNITIYAVEENQESTPVVIQQETTG
  TPRSDTVPSPRDLQFVEVTDVKVTIMWTPPESAVTGYRVDVIPVNLPGEHGQRLPISRNT
  FAEVTGLSPGVTYYFKVFAVSHGRESKPLTAQQTTKLDAPTNLQFVNETDSTVLVRWTPP
  RAQITGYRLTVGLTRRGQPRQYNVGPSVSKYPLRNLQPASEYTVSLVAIKGNQESPKATG
  VFTTLQPGSSIPPYNTEVTETTIVITWTPAPRIGFKLGVRPSQGGEAPREVTSDSGSIVV
  SGLTPGVEYVYTIQVLRDGQERDAPIVNKVVTPLSPPTNLHLEANPDTGVLTVSWERSTT
  PDITGYRITTTPTNGQQGNSLEEVVHADQSSCTFDNLSPGLEYNVSVYTVKDDKESVPIS
  DTIIPEVPQLTDLSFVDITDSSIGLRWTPLNSSTIIGYRITVVAAGEGIPIFEDFVDSSV
  GYYTVTGLEPGIDYDISVITLINGGESAPTTLTQQTAVPPPTDLRFTNIGPDTMRVTWAP
  PPSIDLTNFLVRYSPVKNEEDVAELSISPSDNAVVLTNLLPGTEYVVSVSSVYEQHESTP
  LRGRQKTGLDSPTGIDFSDITANSFTVHWIAPRATITGYRIRHHPEHFSGRPREDRVPHS
  RNSITLTNLTPGTEYVVSIVALNGREESPLLIGQQSTVSDVPRDLEVVAATPTSLLISWD
  APAVTVRYYRITYGETGGNSPVQEFTVPGSKSTATISGLKPGVDYTITVYAVTGRGDSPA
  SSKPISINYRTEIDKPSQMQVTDVQDNSISVKWLPSSSPVTGYRVTTTPKNGPGPTKTKT
  AGPDQTEMTIEGLQPTVEYVVSVYAQNPSGESQPLVQTAVTNIDRPKGLAFTDVDVDSIK
  IAWESPQGQVSRYRVTYSSPEDGIHELFPAPDGEEDTAELQGLRPGSEYTVSVVALHDDM
  ESQPLIGTQSTAIPAPTDLKFTQVTPTSLSAQWTPPNVQLTGYRVRVTPKEKTGPMKEIN
  LAPDSSSVVVSGLMVATKYEVSVYALKDTLTSRPAQGVVTTLENVSPPRRARVTDATETT
  ITISWRTKTETITGFQVDAVPANGQTPIQRTIKPDVRSYTITGLQPGTDYKIYLYTLNDN
  ARSSPVVIDASTAIDAPSNLRFLATTPNSLLVSWQPPRARITGYIIKYEKPGSPPREVVP
  RPRPGVTEATITGLEPGTEYTIYVIALKNNQKSEPLIGRKKTDELPQLVTLPHPNLHGPE
  ILDVPSTVQKTPFVTHPGYDTGNGIQLPGTSGQQPSVGQQMIFEEHGFRRTTPPTTATPI
  RHRPRPYPPNVGEEIQIGHIPREDVDYHLYPHGPGLNPNASTGQEALSQTTISWAPFQDT
  SEYIISCHPVGTDEEPLQFRVPGTSTSATLTGLTRGATYNVIVEALKDQQRHKVREEVVT
  VGNSVNEGLNQPTDDSCFDPYTVSHYAVGDEWERMSESGFKLLCQCLGFGSGHFRCDSSR
  WCHDNGVNYKIGEKWDRQGENGQMMSCTCLGNGKGEFKCDPHEATCYDDGKTYHVGEQWQ
  KEYLGAICSCTCFGGQRGWRCDNCRRPGGEPSPEGTTGQSYNQYSQRYHQRTNTNVNCPI
  ECFMPLDVQADREDSRE
• Function: Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts. Acts as a ligand for the LILRB4 receptor, inhibiting FCGR1A/CD64-mediated monocyte activation ; [Anastellin]: Binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling; Secreted by contracting muscle, induces liver autophagy, a degradative pathway for nutrient mobilization and damage removal, and systemic insulin sensitization via hepatic ITGA5:ITGB1 integrin receptor signaling.
• Tissue Specificity: Expressed in the inner limiting membrane and around blood vessels in the retina (at protein level) . Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2 and Ugl-Y3 are found in urine .
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Bacterial invasion of epithelial cells (hsa05100)
  Yersinia infection (hsa05135)
  Amoebiasis (hsa05146)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Extracellular matrix organization (R-HSA-1474244)
  Fibronectin matrix formation (R-HSA-1566977)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Integrin cell surface interactions (R-HSA-216083)
  Syndecan interactions (R-HSA-3000170)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  MAP2K and MAPK activation (R-HSA-5674135)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  MET activates PTK2 signaling (R-HSA-8874081)
  Post-translational protein phosphorylation (R-HSA-8957275)
  GPER1 signaling (R-HSA-9634597)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  ALK mutants bind TKIs (R-HSA-9700645)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spondylometaphyseal dysplasia, 'corner fracture' type	DIS2MS2B	Definitive	Autosomal dominant	[1]
Glomerulopathy with fibronectin deposits 2	DISVU8V0	Strong	Autosomal dominant	[2]
Fibronectin glomerulopathy	DISKTESP	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Fibronectin (FN1) increases the Investigations ADR of Menadione.	[72]
Vinblastine	DM5TVS3	Approved	Fibronectin (FN1) affects the response to substance of Vinblastine.	[73]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fibronectin (FN1).	[3]
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the phosphorylation of Fibronectin (FN1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fibronectin (FN1).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibronectin (FN1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fibronectin (FN1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibronectin (FN1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fibronectin (FN1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibronectin (FN1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fibronectin (FN1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fibronectin (FN1).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Fibronectin (FN1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fibronectin (FN1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fibronectin (FN1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Fibronectin (FN1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fibronectin (FN1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fibronectin (FN1).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Fibronectin (FN1).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fibronectin (FN1).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Fibronectin (FN1).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Fibronectin (FN1).	[20]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Fibronectin (FN1).	[21]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Fibronectin (FN1).	[22]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Fibronectin (FN1).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Fibronectin (FN1).	[24]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of Fibronectin (FN1).	[25]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Fibronectin (FN1).	[26]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Fibronectin (FN1).	[24]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Fibronectin (FN1).	[27]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Fibronectin (FN1).	[28]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Fibronectin (FN1).	[29]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Fibronectin (FN1).	[30]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Fibronectin (FN1).	[31]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Fibronectin (FN1).	[32]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Fibronectin (FN1).	[33]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Fibronectin (FN1).	[34]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Fibronectin (FN1).	[35]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Fibronectin (FN1).	[37]
Artesunate	DMR27C8	Approved	Artesunate decreases the expression of Fibronectin (FN1).	[39]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Fibronectin (FN1).	[37]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus increases the expression of Fibronectin (FN1).	[40]
Bleomycin	DMNER5S	Approved	Bleomycin increases the expression of Fibronectin (FN1).	[41]
Phenylephrine	DMZHUO5	Approved	Phenylephrine increases the expression of Fibronectin (FN1).	[35]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid decreases the expression of Fibronectin (FN1).	[42]
Ketamine	DMT5HA4	Approved	Ketamine increases the expression of Fibronectin (FN1).	[43]
Aripiprazole	DM3NUMH	Approved	Aripiprazole decreases the expression of Fibronectin (FN1).	[44]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Fibronectin (FN1).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibronectin (FN1).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Fibronectin (FN1).	[47]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Fibronectin (FN1).	[48]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Fibronectin (FN1).	[49]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Fibronectin (FN1).	[50]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fibronectin (FN1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fibronectin (FN1).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fibronectin (FN1).	[52]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Fibronectin (FN1).	[53]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Fibronectin (FN1).	[54]
Tetramethylpyrazine	DMC0WNB	Discontinued in Phase 2	Tetramethylpyrazine decreases the expression of Fibronectin (FN1).	[55]
Piperlongumine	DMIZCOE	Preclinical	Piperlongumine decreases the expression of Fibronectin (FN1).	[57]
HSDB-41	DMR8VJA	Preclinical	HSDB-41 increases the expression of Fibronectin (FN1).	[58]
Calphostin C	DM9X2D0	Terminated	Calphostin C affects the expression of Fibronectin (FN1).	[59]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Fibronectin (FN1).	[61]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Fibronectin (FN1).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fibronectin (FN1).	[62]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Fibronectin (FN1).	[63]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Fibronectin (FN1).	[64]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Fibronectin (FN1).	[65]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Fibronectin (FN1).	[66]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Fibronectin (FN1).	[67]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Fibronectin (FN1).	[68]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Fibronectin (FN1).	[69]
Chrysin	DM7V2LG	Investigative	Chrysin increases the expression of Fibronectin (FN1).	[69]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Fibronectin (FN1).	[69]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Fibronectin (FN1).	[70]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Fibronectin (FN1).	[69]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of Fibronectin (FN1).	[24]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Fibronectin (FN1).	[51]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Fibronectin (FN1).	[51]
3-aminobenzamide	DM7P3IZ	Investigative	3-aminobenzamide decreases the expression of Fibronectin (FN1).	[61]
brucine	DM50RUD	Investigative	brucine decreases the expression of Fibronectin (FN1).	[71]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Vitamin A	DMJ2AH4	Approved	Vitamin A decreases the secretion of Fibronectin (FN1).	[38]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the secretion of Fibronectin (FN1).	[56]

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