Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVYH2DH)

DOT Name	C-terminal-binding protein 1 (CTBP1)
Synonyms	CtBP1; EC 1.1.1.-
Gene Name	CTBP1
Related Disease	Adenoma ( ) Advanced cancer ( ) Alopecia ( ) Alzheimer disease ( ) B-cell neoplasm ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Cerebellar ataxia ( ) Colorectal carcinoma ( ) Dyspepsia ( ) Endometrial carcinoma ( ) Epithelial ovarian cancer ( ) Fanconi anemia complementation group A ( ) Fanconi's anemia ( ) Glioma ( ) Hepatocellular carcinoma ( ) Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome ( ) Lung adenocarcinoma ( ) Metastatic prostate carcinoma ( ) Myelodysplastic syndrome ( ) Neoplasm ( ) Non-insulin dependent diabetes ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) High blood pressure ( ) Metastatic malignant neoplasm ( ) Movement disorder ( ) Prostate cancer ( ) Prostate carcinoma ( ) Colorectal neoplasm ( ) Adult glioblastoma ( ) Familial adenomatous polyposis ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Intellectual disability ( ) Invasive ductal breast carcinoma ( ) Melanoma ( ) Prostate neoplasm ( ) Stomach cancer ( )
UniProt ID	CTBP1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1MX3; 4LCE; 4U6Q; 4U6S; 6CDF; 6CDR; 6V89; 6V8A; 7KWM; 8ARI
EC Number	1.1.1.-
Pfam ID	PF00389 ; PF02826
Sequence	MGSSHLLNKGLPLGVRPPIMNGPLHPRPLVALLDGRDCTVEMPILKDVATVAFCDAQSTQ EIHEKVLNEAVGALMYHTITLTREDLEKFKALRIIVRIGSGFDNIDIKSAGDLGIAVCNV PAASVEETADSTLCHILNLYRRATWLHQALREGTRVQSVEQIREVASGAARIRGETLGII GLGRVGQAVALRAKAFGFNVLFYDPYLSDGVERALGLQRVSTLQDLLFHSDCVTLHCGLN EHNHHLINDFTVKQMRQGAFLVNTARGGLVDEKALAQALKEGRIRGAALDVHESEPFSFS QGPLKDAPNLICTPHAAWYSEQASIEMREEAAREIRRAITGRIPDSLKNCVNKDHLTAAT HWASMDPAVVHPELNGAAYRYPPGVVGVAPTGIPAAVEGIVPSAMSLSHGLPPVAHPPHA PSPGQTVKPEADRDHASDQL
Function	Corepressor targeting diverse transcription regulators such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation.
Tissue Specificity	Expressed in germinal center B-cells.
KEGG Pathway	Wnt sig.ling pathway (hsa04310 ) Notch sig.ling pathway (hsa04330 ) Pathways in cancer (hsa05200 ) Chronic myeloid leukemia (hsa05220 )
Reactome Pathway	SUMOylation of transcription cofactors (R-HSA-3899300 ) Repression of WNT target genes (R-HSA-4641265 ) Signaling by TCF7L2 mutants (R-HSA-5339700 ) Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
BioCyc Pathway	MetaCyc:ENSG00000159692-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alopecia	DIS37HU4	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Dyspepsia	DISYEEY6	Strong	Biomarker	[4]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Altered Expression	[13]
Fanconi's anemia	DISGW6Q8	Strong	Altered Expression	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome	DISEXBDZ	Strong	Autosomal dominant	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[20]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[4]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[12]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[12]
High blood pressure	DISY2OHH	moderate	Biomarker	[21]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[22]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[23]
Prostate cancer	DISF190Y	moderate	Biomarker	[24]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[24]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[10]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[25]
Familial adenomatous polyposis	DISW53RE	Limited	Biomarker	[10]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[26]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[25]
Intellectual disability	DISMBNXP	Limited	Biomarker	[25]
Invasive ductal breast carcinoma	DIS43J58	Limited	Altered Expression	[27]
Melanoma	DIS1RRCY	Limited	Altered Expression	[28]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[24]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[26]
------------------------------------------------------------------------------------


⏷ Show the Full List of 43 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

15 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 C-terminal-binding protein 1 (CTBP1).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-terminal-binding protein 1 (CTBP1).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of C-terminal-binding protein 1 (CTBP1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of C-terminal-binding protein 1 (CTBP1).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of C-terminal-binding protein 1 (CTBP1).	[33]
Selenium	DM25CGV	Approved	Selenium increases the expression of C-terminal-binding protein 1 (CTBP1).	[35]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of C-terminal-binding protein 1 (CTBP1).	[32]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of C-terminal-binding protein 1 (CTBP1).	[36]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of C-terminal-binding protein 1 (CTBP1).	[37]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of C-terminal-binding protein 1 (CTBP1).	[39]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of C-terminal-binding protein 1 (CTBP1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of C-terminal-binding protein 1 (CTBP1).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of C-terminal-binding protein 1 (CTBP1).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-terminal-binding protein 1 (CTBP1).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of C-terminal-binding protein 1 (CTBP1).	[45]
------------------------------------------------------------------------------------


⏷ Show the Full List of 15 Drug(s)

3 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 C-terminal-binding protein 1 (CTBP1).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of C-terminal-binding protein 1 (CTBP1).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of C-terminal-binding protein 1 (CTBP1).	[41]
------------------------------------------------------------------------------------

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 1 (CTBP1).	[38]
------------------------------------------------------------------------------------

References

1	A two-step model for colon adenoma initiation and progression caused by APC loss.Cell. 2009 May 15;137(4):623-34. doi: 10.1016/j.cell.2009.02.037.
2	Identification of common differentially-expressed miRNAs in ovarian cancer cells and their exosomes compared with normal ovarian surface epithelial cell cells.Oncol Lett. 2018 Aug;16(2):2391-2401. doi: 10.3892/ol.2018.8954. Epub 2018 Jun 12.
3	CtBP1 overexpression in keratinocytes perturbs skin homeostasis.J Invest Dermatol. 2014 May;134(5):1323-1331. doi: 10.1038/jid.2013.504. Epub 2013 Nov 26.
4	Structural elucidation and bioactivities of a novel arabinogalactan from Coreopsis tinctoria.Carbohydr Polym. 2019 Sep 1;219:219-228. doi: 10.1016/j.carbpol.2019.05.019. Epub 2019 May 7.
5	CTBP1 Confers Protection for Hippocampal and Cortical Neurons in Rat Models of Alzheimer's Disease.Neuroimmunomodulation. 2019;26(3):139-152. doi: 10.1159/000500942. Epub 2019 Jul 24.
6	The CtBP1-p300-FOXO3a transcriptional complex represses the expression of the apoptotic regulators Bax and Bim in human osteosarcoma cells.J Cell Physiol. 2019 Dec;234(12):22365-22377. doi: 10.1002/jcp.28802. Epub 2019 May 9.
7	Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein.Cell Death Dis. 2019 Sep 18;10(10):689. doi: 10.1038/s41419-019-1892-7.
8	CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.Oncotarget. 2016 Apr 5;7(14):18798-811. doi: 10.18632/oncotarget.7711.
9	Reliability and discriminant validity of ataxia rating scales in early onset ataxia.Dev Med Child Neurol. 2017 Apr;59(4):427-432. doi: 10.1111/dmcn.13291. Epub 2016 Oct 21.
10	Adenomatous polyposis coli control of C-terminal binding protein-1 stability regulates expression of intestinal retinol dehydrogenases.J Biol Chem. 2006 Dec 8;281(49):37828-35. doi: 10.1074/jbc.M602119200. Epub 2006 Oct 6.
11	Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition.Cell Physiol Biochem. 2017;44(6):2357-2367. doi: 10.1159/000486123. Epub 2017 Dec 15.
12	Active-Site Tryptophan, the Target of Antineoplastic C-Terminal Binding Protein Inhibitors, Mediates Inhibitor Disruption of CtBP Oligomerization and Transcription Coregulatory Activities.Mol Pharmacol. 2019 Jul;96(1):99-108. doi: 10.1124/mol.118.114363. Epub 2019 Apr 29.
13	The Fanconi anemia pathway has a dual function in Dickkopf-1 transcriptional repression.Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2152-7. doi: 10.1073/pnas.1314226111. Epub 2014 Jan 27.
14	C-Terminal Binding Protein is Involved in Promoting to the Carcinogenesis of Human Glioma.Mol Neurobiol. 2017 Oct;54(8):6121-6132. doi: 10.1007/s12035-016-0159-x. Epub 2016 Oct 3.
15	Evaluation of Circulatory RNA-Based Biomarker Panel in Hepatocellular Carcinoma.Mol Diagn Ther. 2016 Jun;20(3):265-77. doi: 10.1007/s40291-016-0200-9.
16	A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects. Neurogenetics. 2016 Jul;17(3):173-8. doi: 10.1007/s10048-016-0482-4. Epub 2016 Apr 19.
17	CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma.Oncol Rep. 2019 Jul;42(1):67-78. doi: 10.3892/or.2019.7142. Epub 2019 May 2.
18	Role of transcriptional corepressor CtBP1 in prostate cancer progression.Neoplasia. 2012 Oct;14(10):905-14. doi: 10.1593/neo.121192.
19	AML1-FOG2 fusion protein in myelodysplasia.Blood. 2005 Jun 1;105(11):4523-6. doi: 10.1182/blood-2004-07-2762. Epub 2005 Feb 10.
20	CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome.Int J Cancer. 2019 Mar 1;144(5):1115-1127. doi: 10.1002/ijc.31773. Epub 2018 Oct 9.
21	Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1.Circulation. 2016 Oct 11;134(15):1105-1121. doi: 10.1161/CIRCULATIONAHA.116.023171. Epub 2016 Aug 25.
22	miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells.Oncol Res. 2018 Jan 19;26(1):1-8. doi: 10.3727/096504016X14772410356982. Epub 2017 Nov 29.
23	De novo CTBP1 variant is associated with decreased mitochondrial respiratory chain activities.Neurol Genet. 2017 Sep 22;3(5):e187. doi: 10.1212/NXG.0000000000000187. eCollection 2017 Oct.
24	CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice.Cell Death Dis. 2019 Apr 1;10(4):299. doi: 10.1038/s41419-019-1535-z.
25	A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity.Neurogenetics. 2019 Aug;20(3):129-143. doi: 10.1007/s10048-019-00578-1. Epub 2019 Apr 30.
26	C-terminal of E1A binding protein 1 enhances the migration of gastric epithelial cells and has a clinicopathologic significance in human gastric carcinoma.Onco Targets Ther. 2019 Jul 2;12:5189-5200. doi: 10.2147/OTT.S203479. eCollection 2019.
27	Transcriptional down-regulation of Brca1 and E-cadherin by CtBP1 in breast cancer.Mol Carcinog. 2012 Jun;51(6):500-7. doi: 10.1002/mc.20813. Epub 2011 Jun 16.
28	CtBP1 is expressed in melanoma and represses the transcription of p16INK4a and Brca1.J Invest Dermatol. 2013 May;133(5):1294-301. doi: 10.1038/jid.2012.487. Epub 2013 Jan 10.
29	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
30	Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
31	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
32	Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
33	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.
34	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.
35	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.
36	Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
37	Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
38	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.
39	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.
40	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.
41	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.
42	Unique bisphenol A transcriptome in prostate cancer: novel effects on ERbeta expression that correspond to androgen receptor mutation status. Environ Health Perspect. 2007 Nov;115(11):1646-53. doi: 10.1289/ehp.10283.
43	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
44	Effect of chemical mutagens and carcinogens on gene expression profiles in human TK6 cells. PLoS One. 2012;7(6):e39205. doi: 10.1371/journal.pone.0039205. Epub 2012 Jun 18.
45	Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.