Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT74IAG2)

• DOT Name: Protein furry homolog (FRY)
• Gene Name: FRY
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Congestive heart failure
  Intellectual disability
  Lung adenocarcinoma
  Narcolepsy
  Neoplasm
  Non-insulin dependent diabetes
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Pancreatic cancer
  Parkinson disease
  Prostate carcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
• UniProt ID: FRY_HUMAN
• Pfam ID: PF19421 ; PF14225 ; PF14228 ; PF14222
• Sequence:
  MASQQDSGFFEISIKYLLKSWSNTSPVGNGYIKPPVPPASGTHREKGPPTMLPINVDPDS
  KPGEYVLKSLFVNFTTQAERKIRIIMAEPLEKPLTKSLQRGEDPQFDQVISSMSSLSEYC
  LPSILRTLFDWYKRQNGIEDESHEYRPRTSNKSKSDEQQRDYLMERRDLAIDFIFSLVLI
  EVLKQIPLHPVIDSLIHDVINLAFKHFKYKEGYLGPNTGNMHIVADLYAEVIGVLAQAKF
  PAVKKKFMAELKELRHKEQNPYVVQSIISLIMGMKFFRIKMYPVEDFEASLQFMQECAHY
  FLEVKDKDIKHALAGLFVEILVPVAAAVKNEVNVPCLRNFVESLYDTTLELSSRKKHSLA
  LYPLVTCLLCVSQKQLFLNRWHIFLNNCLSNLKNKDPKMARVALESLYRLLWVYMIRIKC
  ESNTATQSRLITIITTLFPKGSRGVVPRDMPLNIFVKIIQFIAQERLDFAMKEIIFDFLC
  VGKPAKAFSLNPERMNIGLRAFLVIADSLQQKDGEPPMPVTGAVLPSGNTLRVKKTYLSK
  TLTEEEAKMIGMSLYYSQVRKAVDNILRHLDKEVGRCMMLTNVQMLNKEPEDMITGERKP
  KIDLFRTCVAAIPRLLPDGMSKLELIDLLARLSIHMDDELRHIAQNSLQGLLVDFSDWRE
  DVLFGFTNFLLREVNDMHHTLLDSSLKLLLQLLTQWKLVIQTQGKVYEQANKIRNSELIA
  NGSSHRIQSERGPHCSVLHAVEGFALVLLCSFQVATRKLSVLILKEIRALFIALGQPEDD
  DRPMIDVMDQLSSSILESFIHVAVSDSATLPLTHNVDLQWLVEWNAVLVNSHYDVKSPSH
  VWIFAQSVKDPWVLCLFSFLRQENLPKHCPTALSYAWPYAFTRLQSVMPLVDPNSPINAK
  KTSTAGSGDNYVTLWRNYLILCFGVAKPSIMSPGHLRASTPEIMATTPDGTVSYDNKAIG
  TPSVGVLLKQLVPLMRLESIEITESLVLGFGRTNSLVFRELVEELHPLMKEALERRPENK
  KRRERRDLLRLQLLRIFELLADAGVISDSTNGALERDTLALGALFLEYVDLTRMLLEAEN
  DKEVEILKDIRAHFSAMVANLIQCVPVHHRRFLFPQQSLRHHLFILFSQWAGPFSIMFTP
  LDRYSDRNHQITRYQYCALKAMSAVLCCGPVFDNVGLSPDGYLYKWLDNILACQDLRVHQ
  LGCEVVVLLLELNPDQINLFNWAIDRCYTGSYQLASGCFKAIATVCGSRNYPFDIVTLLN
  LVLFKASDTNREIYEISMQLMQILEAKLFVYSKKVAEQRPGSILYGTHGPLPPLYSVSLA
  LLSCELARMYPELTLPLFSEVSQRFPTTHPNGRQIMLTYLLPWLHNIELVDSRLLLPGSS
  PSSPEDEVKDREGDVTASHGLRGNGWGSPEATSLVLNNLMYMTAKYGDEVPGPEMENAWN
  ALANNEKWSNNLRITLQFLISLCGVSSDTVLLPYIKKVAIYLCRNNTIQTMEELLFELQQ
  TEPVNPIVQHCDNPPFYRFTASSKASAAASGTTSSSNTVVAGQENFPDAEENKILKESDE
  RFSNVIRAHTRLESRYSNSSGGSYDEDKNDPISPYTGWLLTITETKQPQPLPMPCTGGCW
  APLVDYLPETITPRGPLHRCNIAVIFMTEMVVDHSVREDWALHLPLLLHAVFLGLDHYRP
  EVFEHSKKLLLHLLIALSCNSNFHSIASVLLQTREMGEAKTLTVQPAYQPEYLYTGGFDF
  LREDQSSPVPDSGLSSSSTSSSISLGGSSGNLPQMTQEVEDVDTAAETDEKANKLIEFLT
  TRAFGPLWCHEDITPKNQNSKSAEQLTNFLRHVVSVFKDSKSGFHLEHQLSEVALQTALA
  SSSRHYAGRSFQIFRALKQPLSAHALSDLLSRLVEVIGEHGDEIQGYVMEALLTLEAAVD
  NLSDCLKNSDLLTVLSRSSSPDLSSSSKLTASRKSTGQLNMNPGTTSGNTATAERSRHQR
  SFSVPKKFGVIDRSSDPPRSATLDRIQACTQQGLSSKTRSSSSLKDSLTDPSHINHPTNL
  LATIFWVTVALMESDFEFEYLMALRLLSRLLAHMPLDKAENREKLEKLQAQLKWADFSGL
  QQLLLKGFTSLTTTDLTLQLFSLLTPVSKISMVDASHAIGFPLNVLCLLPQLIQHFENPN
  QFCKDIAERIAQVCLEEKNPKLSNLAHVMTLYKTHSYTRDCATWVNVVCRYLHEAYADIT
  LNMVTYLAELLEKGLPSVQQPLLQVIYSLLSYMDLSVVPVKQFNVEVLKTIEKYVQSVHW
  REALNILKLVVSRSASLVLPSYQHSDLSKIEIHRVWTSASKELPGKTLDFHFDISETPII
  GRRYDELQNSSGRDGKPRAMAVTRSTSSTSSGSNSNVLVPVSWKRPQYSQKRTKEKLVHV
  LSLCGQEVGLSKNPSVIFSSCGDLDLLEHQTSLVSSEDGAREQENMDDTNSEQQFRVFRD
  FDFLDVELEDGEGESMDNFNWGVRRRSLDSLDKCDMQILEERQLSGSTPSLNKMHHEDSD
  ESSEEEDLTASQILEHSDLIMTLSPSEETNPMELLTTACDSTPAEPHSFNTRMSSFDASL
  PDMNNLQISEGSKAEAVREEEDTTVHEDDLSSSINELPAAFECSDSFSLDMTEGEEKGNR
  ALDQFTLASFGEGDRGVSPPPSPFFSAILAAFQPAACDDAEEAWRSHINQLMCDSDGSCA
  VYTFHVFSSLFKNIQKRFCFLTCDAASYLGDNLRGIGSKFVSSSQMLTSCSECPTLFVDA
  ETLLSCGLLDKLKFSVLELQEYLDTYNNRKEATLSWLANCKATFAGGSRDGVITCQPGDS
  EEKQLELCQRLYKLHFQLLLLFQSYCKLIGQVHEVSSMPELLNMSRELSDLKKHLKEASA
  VIAADPLYSDGAWSEPTFTSTEAAIQSMLECLKNNELGKALRQIRECRSLWPNDIFGSSS
  DDEVQTLLNIYFRHQTLGQTGTYALVGSNQSLTEICTKLMELNMEIRDMIRRAQSYRVLT
  TFLPDSSVSGTSL
• Function: Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis. May function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Cardiac failure	DISDC067	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[5]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[5]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[4]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[5]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[8]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[5]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Genetic Variation	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[5]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[10]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[11]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[11]

22 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 Protein furry homolog (FRY).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein furry homolog (FRY).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein furry homolog (FRY).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein furry homolog (FRY).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein furry homolog (FRY).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein furry homolog (FRY).	[17]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein furry homolog (FRY).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein furry homolog (FRY).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Protein furry homolog (FRY).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein furry homolog (FRY).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein furry homolog (FRY).	[22]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein furry homolog (FRY).	[23]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Protein furry homolog (FRY).	[24]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein furry homolog (FRY).	[25]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein furry homolog (FRY).	[19]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein furry homolog (FRY).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein furry homolog (FRY).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein furry homolog (FRY).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein furry homolog (FRY).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein furry homolog (FRY).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein furry homolog (FRY).	[31]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Protein furry homolog (FRY).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein furry homolog (FRY).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein furry homolog (FRY).	[30]

References

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• [3] Fry Is Required for Mammary Gland Development During Pregnant Periods and Affects the Morphology and Growth of Breast Cancer Cells.Front Oncol. 2019 Nov 21;9:1279. doi: 10.3389/fonc.2019.01279. eCollection 2019.
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• [11] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [12] 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.
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• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [19] 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.
• [20] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [23] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [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] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [26] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
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• [28] 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.
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• [32] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.