Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMYQ3CM)

DOT Name Zinc finger E-box-binding homeobox 2
Synonyms Smad-interacting protein 1; SMADIP1; Zinc finger homeobox protein 1b
Gene Name ZEB2
Related Disease
Mowat-Wilson syndrome ( )
UniProt ID
ZEB2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2DA7
Pfam ID
PF00096 ; PF05605 ; PF12874
Sequence
MKQPIMADGPRCKRRKQANPRRKNVVNYDNVVDTGSETDEEDKLHIAEDDGIANPLDQET
SPASVPNHESSPHVSQALLPREEEEDEIREGGVEHPWHNNEILQASVDGPEEMKEDYDTM
GPEATIQTAINNGTVKNANCTSDFEEYFAKRKLEERDGHAVSIEEYLQRSDTAIIYPEAP
EELSRLGTPEANGQEENDLPPGTPDAFAQLLTCPYCDRGYKRLTSLKEHIKYRHEKNEEN
FSCPLCSYTFAYRTQLERHMVTHKPGTDQHQMLTQGAGNRKFKCTECGKAFKYKHHLKEH
LRIHSGEKPYECPNCKKRFSHSGSYSSHISSKKCIGLISVNGRMRNNIKTGSSPNSVSSS
PTNSAITQLRNKLENGKPLSMSEQTGLLKIKTEPLDFNDYKVLMATHGFSGTSPFMNGGL
GATSPLGVHPSAQSPMQHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKA
EEISKLKGYHMKDPCSQPEEQGVTSPNIPPVGLPVVSHNGATKSIIDYTLEKVNEAKACL
QSLTTDSRRQISNIKKEKLRTLIDLVTDDKMIENHNISTPFSCQFCKESFPGPIPLHQHE
RYLCKMNEEIKAVLQPHENIVPNKAGVFVDNKALLLSSVLSEKGMTSPINPYKDHMSVLK
AYYAMNMEPNSDELLKISIAVGLPQEFVKEWFEQRKVYQYSNSRSPSLERSSKPLAPNSN
PPTKDSLLPRSPVKPMDSITSPSIAELHNSVTNCDPPLRLTKPSHFTNIKPVEKLDHSRS
NTPSPLNLSSTSSKNSHSSSYTPNSFSSEELQAEPLDLSLPKQMKEPKSIIATKNKTKAS
SISLDHNSVSSSSENSDEPLNLTFIKKEFSNSNNLDNKSTNPVFSMNPFSAKPLYTALPP
QSAFPPATFMPPVQTSIPGLRPYPGLDQMSFLPHMAYTYPTGAATFADMQQRRKYQRKQG
FQGELLDGAQDYMSGLDDMTDSDSCLSRKKIKKTESGMYACDLCDKTFQKSSSLLRHKYE
HTGKRPHQCQICKKAFKHKHHLIEHSRLHSGEKPYQCDKCGKRFSHSGSYSQHMNHRYSY
CKREAEEREAAEREAREKGHLEPTELLMNRAYLQSITPQGYSDSEERESMPRDGESEKEH
EKEGEDGYGKLGRQDGDEEFEEEEEESENKSMDTDPETIRDEEETGDHSMDDSSEDGKME
TKSDHEEDNMEDGM
Function Transcriptional inhibitor that binds to DNA sequence 5'-CACCT-3' in different promoters. Represses transcription of E-cadherin. Represses expression of MEOX2.
KEGG Pathway
MicroR.s in cancer (hsa05206 )
Reactome Pathway
Formation of the anterior neural plate (R-HSA-9823739 )
Formation of the posterior neural plate (R-HSA-9832991 )
Regulation of CDH11 gene transcription (R-HSA-9762293 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mowat-Wilson syndrome DISD1AW7 Definitive Autosomal dominant [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 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 Zinc finger E-box-binding homeobox 2. [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Zinc finger E-box-binding homeobox 2. [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Zinc finger E-box-binding homeobox 2. [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Zinc finger E-box-binding homeobox 2. [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Zinc finger E-box-binding homeobox 2. [6]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Zinc finger E-box-binding homeobox 2. [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Zinc finger E-box-binding homeobox 2. [8]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Zinc finger E-box-binding homeobox 2. [9]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Zinc finger E-box-binding homeobox 2. [10]
Resveratrol DM3RWXL Phase 3 Resveratrol affects the expression of Zinc finger E-box-binding homeobox 2. [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Zinc finger E-box-binding homeobox 2. [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Zinc finger E-box-binding homeobox 2. [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Zinc finger E-box-binding homeobox 2. [9]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Zinc finger E-box-binding homeobox 2. [17]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Zinc finger E-box-binding homeobox 2. [18]
Nitrobenzanthrone DMN6L70 Investigative Nitrobenzanthrone decreases the expression of Zinc finger E-box-binding homeobox 2. [19]
NADA DM3ORGM Investigative NADA decreases the expression of Zinc finger E-box-binding homeobox 2. [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 17 Drug(s)
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 decreases the methylation of Zinc finger E-box-binding homeobox 2. [12]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Zinc finger E-box-binding homeobox 2. [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Zinc finger E-box-binding homeobox 2. [16]
------------------------------------------------------------------------------------

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 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.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
8 Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-/Smad signaling pathways. Cell Biol Toxicol. 2021 Jun;37(3):479-496. doi: 10.1007/s10565-020-09562-0. Epub 2020 Oct 17.
9 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
10 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
11 Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the epigenetic inhibition of ZEB1 expression. Oncotarget. 2016 Mar 15;7(11):12137-49. doi: 10.18632/oncotarget.7763.
12 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.
13 Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
14 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
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 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
17 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
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 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
20 N-arachidonoyl dopamine inhibits epithelial-mesenchymal transition of breast cancer cells through ERK signaling and decreasing the cellular cholesterol. J Biochem Mol Toxicol. 2021 Apr;35(4):e22693. doi: 10.1002/jbt.22693. Epub 2021 Jan 4.