Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGZGT87)

DOT Name	C-terminal-binding protein 2 (CTBP2)
Synonyms	CtBP2
Gene Name	CTBP2
Related Disease	Bone osteosarcoma ( ) Osteosarcoma ( ) Adenoma ( ) Anorexia nervosa cachexia ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma of esophagus ( ) Epithelial ovarian cancer ( ) Esophageal cancer ( ) Esophageal squamous cell carcinoma ( ) Glioma ( ) Hepatocellular carcinoma ( ) leukaemia ( ) Leukemia ( ) Lupus ( ) Nasopharyngeal carcinoma ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Polyp ( ) Respiratory disease ( ) Systemic lupus erythematosus ( ) Gastric cancer ( ) Prostate carcinoma ( ) Stomach cancer ( ) Advanced cancer ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Neuroblastoma ( ) Prostate cancer ( ) Prostate neoplasm ( )
UniProt ID	CTBP2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2OME; 4LCJ; 6WKW
Pfam ID	PF00389 ; PF02826
Sequence	MALVDKHKVKRQRLDRICEGIRPQIMNGPLHPRPLVALLDGRDCTVEMPILKDLATVAFC DAQSTQEIHEKVLNEAVGAMMYHTITLTREDLEKFKALRVIVRIGSGYDNVDIKAAGELG IAVCNIPSAAVEETADSTICHILNLYRRNTWLYQALREGTRVQSVEQIREVASGAARIRG ETLGLIGFGRTGQAVAVRAKAFGFSVIFYDPYLQDGIERSLGVQRVYTLQDLLYQSDCVS LHCNLNEHNHHLINDFTIKQMRQGAFLVNAARGGLVDEKALAQALKEGRIRGAALDVHES EPFSFAQGPLKDAPNLICTPHTAWYSEQASLEMREAAATEIRRAITGRIPESLRNCVNKE FFVTSAPWSVIDQQAIHPELNGATYRYPPGIVGVAPGGLPAAMEGIIPGGIPVTHNLPTV AHPSQAPSPNQPTKHGDNREHPNEQ
Function	Corepressor targeting diverse transcription regulators. Functions in brown adipose tissue (BAT) differentiation; Isoform 2 probably acts as a scaffold for specialized synapses.
Tissue Specificity	Ubiquitous. Highest levels in heart, skeletal muscle, and pancreas.
KEGG Pathway	Wnt sig.ling pathway (hsa04310 ) Notch sig.ling pathway (hsa04330 ) Pathways in cancer (hsa05200 ) Chronic myeloid leukemia (hsa05220 )
Reactome Pathway	(Name not found ) Signaling by TCF7L2 mutants (R-HSA-5339700 ) Repression of WNT target genes (R-HSA-4641265 )

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
leukaemia	DISS7D1V	Strong	Altered Expression	[11]
Leukemia	DISNAKFL	Strong	Altered Expression	[11]
Lupus	DISOKJWA	Strong	Biomarker	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Polyp	DISRSLYF	Strong	Biomarker	[17]
Respiratory disease	DISGGAGJ	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[19]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[20]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[19]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[21]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[21]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[22]
Prostate cancer	DISF190Y	Limited	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[21]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	C-terminal-binding protein 2 (CTBP2) decreases the response to substance of Arsenic trioxide.	[40]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of C-terminal-binding protein 2 (CTBP2).	[23]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of C-terminal-binding protein 2 (CTBP2).	[27]
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16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-terminal-binding protein 2 (CTBP2).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of C-terminal-binding protein 2 (CTBP2).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of C-terminal-binding protein 2 (CTBP2).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of C-terminal-binding protein 2 (CTBP2).	[28]
Selenium	DM25CGV	Approved	Selenium decreases the expression of C-terminal-binding protein 2 (CTBP2).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of C-terminal-binding protein 2 (CTBP2).	[30]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of C-terminal-binding protein 2 (CTBP2).	[31]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of C-terminal-binding protein 2 (CTBP2).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of C-terminal-binding protein 2 (CTBP2).	[33]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of C-terminal-binding protein 2 (CTBP2).	[34]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of C-terminal-binding protein 2 (CTBP2).	[35]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of C-terminal-binding protein 2 (CTBP2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of C-terminal-binding protein 2 (CTBP2).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of C-terminal-binding protein 2 (CTBP2).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of C-terminal-binding protein 2 (CTBP2).	[38]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of C-terminal-binding protein 2 (CTBP2).	[39]
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⏷ Show the Full List of 16 Drug(s)

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Pyruvic acid	DM7Q41G	Approved	Pyruvic acid affects the localization of C-terminal-binding protein 2 (CTBP2).	[32]
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References

1	C-terminal of E1A binding protein 2 promotes the malignancy of osteosarcoma cells via JAK1/Stat3 signaling.J Cell Commun Signal. 2020 Mar;14(1):67-76. doi: 10.1007/s12079-019-00523-9. Epub 2019 Jun 19.
2	An intestinal stem cell niche in Apc mutated neoplasia targetable by CtBP inhibition.Oncotarget. 2018 Aug 21;9(65):32408-32418. doi: 10.18632/oncotarget.25784. eCollection 2018 Aug 21.
3	Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.Mol Psychiatry. 2017 Feb;22(2):192-201. doi: 10.1038/mp.2016.71. Epub 2016 May 17.
4	C-terminal binding protein-2 promotes cell proliferation and migration in breast cancer via suppression of p16INK4A.Oncotarget. 2017 Apr 18;8(16):26154-26168. doi: 10.18632/oncotarget.15402.
5	Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha.BMC Genomics. 2014 Jun 24;15(1):520. doi: 10.1186/1471-2164-15-520.
6	C-terminal binding protein? mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis.Int J Oncol. 2018 Jul;53(1):167-176. doi: 10.3892/ijo.2018.4367. Epub 2018 Apr 12.
7	C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors.Oncogene. 2013 Aug 15;32(33):3896-903. doi: 10.1038/onc.2012.380. Epub 2012 Sep 3.
8	LncRNA NEAT1 Regulates Cell Viability and Invasion in Esophageal Squamous Cell Carcinoma through the miR-129/CTBP2 Axis.Dis Markers. 2017;2017:5314649. doi: 10.1155/2017/5314649. Epub 2017 Sep 25.
9	MiR-338 suppresses cell proliferation and invasion by targeting CTBP2 in glioma.Cancer Biomark. 2017 Sep 7;20(3):289-297. doi: 10.3233/CBM-170128.
10	HBV Upregulates CtBP2 Expression via the X Gene.Biomed Res Int. 2018 Jul 31;2018:6960573. doi: 10.1155/2018/6960573. eCollection 2018.
11	NGF inhibits human leukemia proliferation by downregulating cyclin A1 expression through promoting acinus/CtBP2 association.Oncogene. 2009 Oct 29;28(43):3825-36. doi: 10.1038/onc.2009.236. Epub 2009 Aug 10.
12	Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells.J Immunol. 2017 Jun 1;198(11):4268-4276. doi: 10.4049/jimmunol.1601705. Epub 2017 Apr 24.
13	A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
14	CtBP-a targetable dependency for tumor-initiating cell activity and metastasis in pancreatic adenocarcinoma.Oncogenesis. 2019 Oct 4;8(10):55. doi: 10.1038/s41389-019-0163-x.
15	CtBP2 promotes proliferation and reduces drug sensitivity in non-small cell lung cancer via the Wnt/-catenin pathway.Neoplasma. 2018 Nov 15;65(6):888-897. doi: 10.4149/neo_2018_171220N828. Epub 2018 Sep 4.
16	BRCA1 expression is epigenetically repressed in sporadic ovarian cancer cells by overexpression of C-terminal binding protein 2.Neoplasia. 2013 Jun;15(6):600-8. doi: 10.1593/neo.121674.
17	Transforming activity and therapeutic targeting of C-terminal-binding protein 2 in Apc-mutated neoplasia.Oncogene. 2017 Aug 17;36(33):4810-4816. doi: 10.1038/onc.2017.106. Epub 2017 Apr 17.
18	Genome-wide association studies identify susceptibility loci affecting respiratory disease in Chinese Erhualian pigs under natural conditions.Anim Genet. 2017 Feb;48(1):30-37. doi: 10.1111/age.12504. Epub 2016 Sep 12.
19	CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric cancer and is associated with poor prognosis.Oncotarget. 2017 Apr 25;8(17):28736-28749. doi: 10.18632/oncotarget.15661.
20	Antimony enhances c-Myc stability in prostate cancer via activating CtBP2-ROCK1 signaling pathway.Ecotoxicol Environ Saf. 2018 Nov 30;164:61-68. doi: 10.1016/j.ecoenv.2018.07.070. Epub 2018 Aug 8.
21	Multiple loci identified in a genome-wide association study of prostate cancer.Nat Genet. 2008 Mar;40(3):310-5. doi: 10.1038/ng.91. Epub 2008 Feb 10.
22	Down-regulation of C-terminal binding protein 2 (CtBP2) inhibits proliferation, migration, and invasion of human SHSY5Y cells in vitro.Neurosci Lett. 2017 Apr 24;647:104-109. doi: 10.1016/j.neulet.2017.02.006. Epub 2017 Feb 6.
23	Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
24	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.
25	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
26	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.
27	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.
28	Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
29	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
30	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.
31	Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
32	Phosphorylation of CtBP1 by cAMP-dependent protein kinase modulates induction of CYP17 by stimulating partnering of CtBP1 and 2. J Biol Chem. 2008 Mar 14;283(11):6925-34. doi: 10.1074/jbc.M708432200. Epub 2008 Jan 9.
33	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
34	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.
35	Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
36	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
37	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
38	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.
39	Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
40	The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.