Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEGV3GO)

• DOT Name: NEDD4-binding protein 2-like 1 (N4BP2L1)
• Gene Name: N4BP2L1
• Related Disease:
  Advanced cancer
  Oral cancer
  Squamous cell carcinoma
• UniProt ID: N42L1_HUMAN
• Pfam ID: PF13671
• Sequence:
  MEDSFLQSFGRLSLQPQQQQQRQRPPRPPPRGTPPRRHSFRKHLYLLRGLPGSGKTTLAR
  QLQHDFPRALIFSTDDFFFREDGAYEFNPDFLEEAHEWNQKRARKAMRNGISPIIIDNTN
  LHAWEMKPYAVMALENNYEVIFREPDTRWKFNVQELARRNIHGVSREKIHRMKERYEHDV
  TFHSVLHAEKPSRMNRNQDRNNALPSNNARYWNSYTEFPNRRAHGGFTNESSYHRRGGCH
  HGY

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Oral cancer	DISLD42D	Limited	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[13]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of NEDD4-binding protein 2-like 1 (N4BP2L1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NEDD4-binding protein 2-like 1 (N4BP2L1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of NEDD4-binding protein 2-like 1 (N4BP2L1).	[17]

References

• [1] NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.Virchows Arch. 2016 Aug;469(2):163-72. doi: 10.1007/s00428-016-1955-4. Epub 2016 May 16.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] 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.
• [9] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 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.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] 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.
• [14] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] 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.
• [18] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.