Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPY8IMS)

DOT Name Filamin A-interacting protein 1-like (FILIP1L)
Synonyms 130 kDa GPBP-interacting protein; 90 kDa GPBP-interacting protein; Protein down-regulated in ovarian cancer 1; DOC-1
Gene Name FILIP1L
Related Disease
Advanced cancer ( )
Atrial fibrillation ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Isolated cleft lip ( )
Neoplasm ( )
Oral cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Age-related macular degeneration ( )
Squamous cell carcinoma ( )
Colorectal carcinoma ( )
Congenital contractural arachnodactyly ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
FIL1L_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF09727
Sequence
MRSRGSDTEGSAQKKFPRHTKGHSFQGPKNMKHRQQDKDSPSESDVILPCPKAEKPHSGN
GHQAEDLSRDDLLFLLSILEGELQARDEVIGILKAEKMDLALLEAQYGFVTPKKVLEALQ
RDAFQAKSTPWQEDIYEKPMNELDKVVEKHKESYRRILGQLLVAEKSRRQTILELEEEKR
KHKEYMEKSDEFICLLEQECERLKKLIDQEIKSQEEKEQEKEKRVTTLKEELTKLKSFAL
MVVDEQQRLTAQLTLQRQKIQELTTNAKETHTKLALAEARVQEEEQKATRLEKELQTQTT
KFHQDQDTIMAKLTNEDSQNRQLQQKLAALSRQIDELEETNRSLRKAEEELQDIKEKISK
GEYGNAGIMAEVEELRKRVLDMEGKDEELIKMEEQCRDLNKRLERETLQSKDFKLEVEKL
SKRIMALEKLEDAFNKSKQECYSLKCNLEKERMTTKQLSQELESLKVRIKELEAIESRLE
KTEFTLKEDLTKLKTLTVMFVDERKTMSEKLKKTEDKLQAASSQLQVEQNKVTTVTEKLI
EETKRALKSKTDVEEKMYSVTKERDDLKNKLKAEEEKGNDLLSRVNMLKNRLQSLEAIEK
DFLKNKLNQDSGKSTTALHQENNKIKELSQEVERLKLKLKDMKAIEDDLMKTEDEYETLE
RRYANERDKAQFLSKELEHVKMELAKYKLAEKTETSHEQWLFKRLQEEEAKSGHLSREVD
ALKEKIHEYMATEDLICHLQGDHSVLQKKLNQQENRNRDLGREIENLTKELERYRHFSKS
LRPSLNGRRISDPQVFSKEVQTEAVDNEPPDYKSLIPLERAVINGQLYEESENQDEDPND
EGSVLSFKCSQSTPCPVNRKLWIPWMKSKEGHLQNGKMQTKPNANFVQPGDLVLSHTPGQ
PLHIKVTPDHVQNTATLEITSPTTESPHSYTSTAVIPNCGTPKQRITILQNASITPVKSK
TSTEDLMNLEQGMSPITMATFARAQTPESCGSLTPERTMSPIQVLAVTGSASSPEQGRSP
EPTEISAKHAIFRVSPDRQSSWQFQRSNSNSSSVITTEDNKIHIHLGSPYMQAVASPVRP
ASPSAPLQDNRTQGLINGALNKTTNKVTSSITITPTATPLPRQSQITVEPLLLPH
Function
Acts as a regulator of the antiangiogenic activity on endothelial cells. When overexpressed in endothelial cells, leads to inhibition of cell proliferation and migration and an increase in apoptosis. Inhibits melanoma growth When expressed in tumor-associated vasculature.
Tissue Specificity
Expressed in endothelial cells, colon and colon cancers. In the colon, expressed in the vasculature and muscularis mucosa. In colon cancer, strongly expressed in tumor stroma and the vasculature (at protein level). Expressed in ovarian epithelial cells. Down-regulated in ovarian cancer.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Atrial fibrillation DIS15W6U Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Genetic Variation [3]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [4]
Isolated cleft lip DIS2O2JV Strong Genetic Variation [5]
Neoplasm DISZKGEW Strong Biomarker [6]
Oral cancer DISLD42D Strong Biomarker [7]
Ovarian cancer DISZJHAP Strong Biomarker [4]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Age-related macular degeneration DIS0XS2C moderate Genetic Variation [8]
Squamous cell carcinoma DISQVIFL moderate Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [6]
Congenital contractural arachnodactyly DISOM1K7 Limited Altered Expression [10]
Prostate cancer DISF190Y Limited Altered Expression [11]
Prostate carcinoma DISMJPLE Limited Altered Expression [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Filamin A-interacting protein 1-like (FILIP1L). [12]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [13]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [15]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [16]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [17]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [18]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [19]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [20]
Progesterone DMUY35B Approved Progesterone increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [21]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [22]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [23]
Malathion DMXZ84M Approved Malathion increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [24]
Azacitidine DMTA5OE Approved Azacitidine decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [25]
Ampicillin DMHWE7P Approved Ampicillin increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [18]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [26]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [28]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [29]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Filamin A-interacting protein 1-like (FILIP1L). [31]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE increases the expression of Filamin A-interacting protein 1-like (FILIP1L). [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 22 Drug(s)

References

1 Reduced expression of FILIP1L, a novel WNT pathway inhibitor, is associated with poor survival, progression and chemoresistance in ovarian cancer.Oncotarget. 2016 Nov 22;7(47):77052-77070. doi: 10.18632/oncotarget.12784.
2 Effectiveness of the Chest Strap Electrocardiogram to Detect Atrial Fibrillation.Am J Cardiol. 2019 May 15;123(10):1643-1648. doi: 10.1016/j.amjcard.2019.02.028. Epub 2019 Feb 23.
3 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
4 Enhanced antitumor effect of biodegradable cationic heparin-polyethyleneimine nanogels delivering FILIP1LC103 gene combined with low-dose cisplatin on ovarian cancer.Oncotarget. 2017 Jul 22;8(44):76432-76442. doi: 10.18632/oncotarget.19464. eCollection 2017 Sep 29.
5 Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
6 Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer.Oncotarget. 2016 Nov 1;7(44):72229-72241. doi: 10.18632/oncotarget.12664.
7 DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells.Cell Rep. 2017 Jul 5;20(1):61-75. doi: 10.1016/j.celrep.2017.06.020.
8 Association of coding and UTR variants in the known regions with wet age-related macular degeneration in Han Chinese population.J Hum Genet. 2018 Oct;63(10):1055-1070. doi: 10.1038/s10038-018-0490-3. Epub 2018 Jul 19.
9 Risk estimation for a malignant transformation of oral lesions by S100A7 and Doc-1 gene expression.Cancer Invest. 2011 Aug;29(7):478-84. doi: 10.3109/07357907.2011.597813.
10 Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma.Ann Hepatol. 2016 Jan-Feb;15(1):71-81. doi: 10.5604/16652681.1184223.
11 CpG island hypermethylation frequently silences FILIP1L isoform 2 expression in prostate cancer.J Urol. 2013 Jan;189(1):329-35. doi: 10.1016/j.juro.2012.08.188. Epub 2012 Nov 20.
12 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.
13 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
14 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
15 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
16 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
17 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
18 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.
19 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
20 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
21 Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
22 Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
23 Identification of troglitazone responsive genes: induction of RTP801 during troglitazone-induced apoptosis in Hep 3B cells. BMB Rep. 2010 Sep;43(9):599-603. doi: 10.5483/BMBRep.2010.43.9.599.
24 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.
25 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
26 Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.
27 Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
28 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
29 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
30 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
31 Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.