Details of Drug Off-Target (DOT)

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

• DOT Name: Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP)
• Synonyms: I kappa-B kinase-interacting protein; IKBKB-interacting protein; IKK-interacting protein
• Gene Name: IKBIP
• Related Disease:
  Advanced cancer
  Barrett esophagus
  Glioma
• UniProt ID: IKIP_HUMAN
• Sequence:
  MSEVKSRKKSGPKGAPAAEPGKRSEGGKTPVARSSGGGGWADPRTCLSLLSLGTCLGLAW
  FVFQQSEKFAKVENQYQLLKLETNEFQQLQSKISLISEKWQKSEAIMEQLKSFQIIAHLK
  RLQEEINEVKTWSNRITEKQDILNNSLTTLSQDITKVDQSTTSMAKDVGLKITSVKTDIR
  RISGLVTDVISLTDSVQELENKIEKVEKNTVKNIGDLLSSSIDRTATLRKTASENSQRIN
  SVKKTLTELKSDFDKHTDRFLSLEGDRAKVLKTVTFANDLKPKVYNLKKDFSRLEPLVND
  LTLRIGRLVTDLLQREKEIAFLSEKISNLTIVQAEIKDIKDEIAHISDMN
• Function: Target of p53/TP53 with pro-apoptotic function.
• Tissue Specificity: Expressed in vein endothelial cells. Isoform 4 is expressed in lung, kidney, spleen, thymus and skeletal muscle.
• Reactome Pathway: Regulation of NF-kappa B signaling (R-HSA-9758274)

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	Strong	Biomarker	[1]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[1]

18 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 Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[17]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP).	[19]

References

• [1] Identification of the potential biomarkers in patients with glioma: a weighted gene co-expression network analysis.Carcinogenesis. 2020 Jul 10;41(6):743-750. doi: 10.1093/carcin/bgz194.
• [2] Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.Clin Gastroenterol Hepatol. 2018 Oct;16(10):1598-1606.e4. doi: 10.1016/j.cgh.2018.03.007. Epub 2018 Mar 15.
• [3] A comparative transcriptomic study on the effects of valproic acid on two different hESCs lines in a neural teratogenicity test system. Toxicol Lett. 2014 Nov 18;231(1):38-44.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Apoptosis, cell cycle progression and gene expression in TP53-depleted HCT116 colon cancer cells in response to short-term 5-fluorouracil treatment. Int J Oncol. 2007 Dec;31(6):1491-500.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [19] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.