Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH1S2P2)

• DOT Name: Formin-binding protein 1-like (FNBP1L)
• Synonyms: Transducer of Cdc42-dependent actin assembly protein 1; Toca-1
• Gene Name: FNBP1L
• Related Disease:
  Bacillary dysentery
  Breast adenocarcinoma
  Breast cancer
  Metastatic malignant neoplasm
  Breast carcinoma
  Breast neoplasm
• UniProt ID: FBP1L_HUMAN
• Pfam ID: PF00611 ; PF00018
• Sequence:
  MSWGTELWDQFDSLDKHTQWGIDFLERYAKFVKERIEIEQNYAKQLRNLVKKYCPKRSSK
  DEEPRFTSCVAFFNILNELNDYAGQREVVAEEMAHRVYGELMRYAHDLKTERKMHLQEGR
  KAQQYLDMCWKQMDNSKKKFERECREAEKAQQSYERLDNDTNATKADVEKAKQQLNLRTH
  MADENKNEYAAQLQNFNGEQHKHFYVVIPQIYKQLQEMDERRTIKLSECYRGFADSERKV
  IPIISKCLEGMILAAKSVDERRDSQMVVDSFKSGFEPPGDFPFEDYSQHIYRTISDGTIS
  ASKQESGKMDAKTTVGKAKGKLWLFGKKPKPQSPPLTPTSLFTSSTPNGSQFLTFSIEPV
  HYCMNEIKTGKPRIPSFRSLKRGWSVKMGPALEDFSHLPPEQRRKKLQQRIDELNRELQK
  ESDQKDALNKMKDVYEKNPQMGDPGSLQPKLAETMNNIDRLRMEIHKNEAWLSEVEGKTG
  GRGDRRHSSDINHLVTQGRESPEGSYTDDANQEVRGPPQQHGHHNEFDDEFEDDDPLPAI
  GHCKAIYPFDGHNEGTLAMKEGEVLYIIEEDKGDGWTRARRQNGEEGYVPTSYIDVTLEK
  NSKGS
• Function: Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. May bind to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promote membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by activating the WASL/N-WASP-WASPIP/WIP complex, the predominant form of WASL/N-WASP in cells. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Essential for autophagy of intracellular bacterial pathogens.
• KEGG Pathway: Shigellosis (hsa05131)
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOJ GTPase cycle (R-HSA-9013409)
  Clathrin-mediated endocytosis (R-HSA-8856828)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[1]
Breast adenocarcinoma	DISMPHJ0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[3]

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 Formin-binding protein 1-like (FNBP1L).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Formin-binding protein 1-like (FNBP1L).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Formin-binding protein 1-like (FNBP1L).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Formin-binding protein 1-like (FNBP1L).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Formin-binding protein 1-like (FNBP1L).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Formin-binding protein 1-like (FNBP1L).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Formin-binding protein 1-like (FNBP1L).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Formin-binding protein 1-like (FNBP1L).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Formin-binding protein 1-like (FNBP1L).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Formin-binding protein 1-like (FNBP1L).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Formin-binding protein 1-like (FNBP1L).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Formin-binding protein 1-like (FNBP1L).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Formin-binding protein 1-like (FNBP1L).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Formin-binding protein 1-like (FNBP1L).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Formin-binding protein 1-like (FNBP1L).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Formin-binding protein 1-like (FNBP1L).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Formin-binding protein 1-like (FNBP1L).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Formin-binding protein 1-like (FNBP1L).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Formin-binding protein 1-like (FNBP1L).	[24]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Formin-binding protein 1-like (FNBP1L).	[25]

3 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 Formin-binding protein 1-like (FNBP1L).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Formin-binding protein 1-like (FNBP1L).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Formin-binding protein 1-like (FNBP1L).	[21]

References

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• [2] Transducer of Cdc42-dependent actin assembly promotes breast cancer invasion and metastasis.Oncogene. 2013 Jun 20;32(25):3080-90. doi: 10.1038/onc.2012.317. Epub 2012 Jul 23.
• [3] Toca-1 is suppressed by p53 to limit breast cancer cell invasion and tumor metastasis.Breast Cancer Res. 2014 Dec 30;16(6):3413. doi: 10.1186/s13058-014-0503-x.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [14] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] 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.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
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• [25] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.