Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPC4ANL)

• DOT Name: Max-binding protein MNT (MNT)
• Synonyms: Class D basic helix-loop-helix protein 3; bHLHd3; Myc antagonist MNT; Protein ROX
• Gene Name: MNT
• Related Disease:
  Advanced cancer
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Classic lissencephaly
  Cytomegalovirus infection
  Dengue
  Hepatocellular carcinoma
  Isolated cleft palate
  Lissencephaly type 1 due to doublecortin gene mutation
  Lung cancer
  Medulloblastoma
  Nasal polyp
  Neoplasm
  Rheumatic fever
  Subcortical band heterotopia
  Carcinoma of liver and intrahepatic biliary tract
  Factor IX deficiency
  Liver cancer
  Melanoma
  Subarachnoid hemorrhage
• UniProt ID: MNT_HUMAN
• Pfam ID: PF00010
• Sequence:
  MSIETLLEAARFLEWQAQQQQRAREEQERLRLEQEREQEQKKANSLARLAHTLPVEEPRM
  EAPPLPLSPPAPPPAPPPPLATPAPLTVIPIPVVTNSPQPLPPPPPLPAAAQPLPLAPRQ
  PALVGAPGLSIKEPAPLPSRPQVPTPAPLLPDSKATIPPNGSPKPLQPLPTPVLTIAPHP
  GVQPQLAPQQPPPPTLGTLKLAPAEEVKSSEQKKRPGGIGTREVHNKLEKNRRAHLKECF
  ETLKRNIPNVDDKKTSNLSVLRTALRYIQSLKRKEKEYEHEMERLAREKIATQQRLAELK
  HELSQWMDVLEIDRVLRQTGQPEDDQASTSTASEGEDNIDEDMEEDRAGLGPPKLSHRPQ
  PELLKSTLPPPSTTPAPLPPHPHPHPHSVALPPAHLPVQQQQPQQKTPLPAPPPPPAAPA
  QTLVPAPAHLVATAGGGSTVIAHTATTHASVIQTVNHVLQGPGGKHIAHIAPSAPSPAVQ
  LAPATPPIGHITVHPATLNHVAHLGSQLPLYPQPVAVSHIAHTLSHQQVNGTAGLGPPAT
  VMAKPAVGAQVVHHPQLVGQTVLNPVTMVTMPSFPVSTLKLA
• Function: Binds DNA as a heterodimer with MAX and represses transcription. Binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[4]
Classic lissencephaly	DISR8S3S	Strong	Biomarker	[5]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[6]
Dengue	DISKH221	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[5]
Lissencephaly type 1 due to doublecortin gene mutation	DIS9ZVA1	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[10]
Nasal polyp	DISLP3XE	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[12]
Rheumatic fever	DISLUF66	Strong	Genetic Variation	[13]
Subcortical band heterotopia	DISHN7JS	Strong	Biomarker	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[14]
Factor IX deficiency	DISHN9SC	moderate	Biomarker	[15]
Liver cancer	DISDE4BI	moderate	Biomarker	[14]
Melanoma	DIS1RRCY	moderate	Biomarker	[16]
Subarachnoid hemorrhage	DISI7I8Y	Limited	Biomarker	[17]

18 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 Max-binding protein MNT (MNT).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Max-binding protein MNT (MNT).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Max-binding protein MNT (MNT).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Max-binding protein MNT (MNT).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Max-binding protein MNT (MNT).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Max-binding protein MNT (MNT).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Max-binding protein MNT (MNT).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Max-binding protein MNT (MNT).	[25]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Max-binding protein MNT (MNT).	[26]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Max-binding protein MNT (MNT).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of Max-binding protein MNT (MNT).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Max-binding protein MNT (MNT).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Max-binding protein MNT (MNT).	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Max-binding protein MNT (MNT).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Max-binding protein MNT (MNT).	[31]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Max-binding protein MNT (MNT).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Max-binding protein MNT (MNT).	[34]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Max-binding protein MNT (MNT).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Max-binding protein MNT (MNT).	[33]

References

• [1] Expression and mutation analysis of genes that encode the Myc antagonists Mad1, Mxi1 and Rox in acute leukaemia.Leuk Lymphoma. 2007 Jun;48(6):1200-7. doi: 10.1080/10428190701342018.
• [2] Surface-based shared and distinct resting functional connectivity in attention-deficit hyperactivity disorder and autism spectrum disorder.Br J Psychiatry. 2019 Jun;214(6):339-344. doi: 10.1192/bjp.2018.248.
• [3] On the difference of micronucleus frequencies in peripheral blood lymphocytes between breast cancer patients and controls.Mutagenesis. 2006 Sep;21(5):313-20. doi: 10.1093/mutage/gel035. Epub 2006 Aug 22.
• [4] The human ROX gene: genomic structure and mutation analysis in human breast tumors.Genomics. 1998 Apr 15;49(2):275-82. doi: 10.1006/geno.1998.5241.
• [5] Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller-Dieker syndrome.Hum Mol Genet. 2004 May 15;13(10):1057-67. doi: 10.1093/hmg/ddh116. Epub 2004 Mar 17.
• [6] Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes.J Immunol. 1989 Nov 15;143(10):3343-52.
• [7] Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia.Am J Trop Med Hyg. 2016 Aug 3;95(2):315-21. doi: 10.4269/ajtmh.15-0492. Epub 2016 May 16.
• [8] MNT inhibits the migration of human hepatocellular carcinoma SMMC7721 cells.Biochem Biophys Res Commun. 2012 Feb 3;418(1):93-7. doi: 10.1016/j.bbrc.2011.12.140. Epub 2012 Jan 5.
• [9] Molecular analysis of a Myc antagonist, ROX/Mnt, at 17p13.3 in human lung cancers.Jpn J Cancer Res. 1998 Apr;89(4):347-51. doi: 10.1111/j.1349-7006.1998.tb00569.x.
• [10] Analysis of transcripts from 17p13.3 in medulloblastoma suggests ROX/MNT as a potential tumour suppressor gene.Eur J Cancer. 2004 Nov;40(16):2525-32. doi: 10.1016/j.ejca.2004.08.005.
• [11] Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis.Int J Mol Sci. 2019 Nov 1;20(21):5461. doi: 10.3390/ijms20215461.
• [12] Cytotoxicity profiling of deep eutectic solvents to human skin cells.Sci Rep. 2019 Mar 8;9(1):3932. doi: 10.1038/s41598-019-39910-y.
• [13] The families of patients with acute rheumatic fever or glomerulonephritis in Trinidad.Am J Epidemiol. 1977 Aug;106(2):130-8. doi: 10.1093/oxfordjournals.aje.a112442.
• [14] Identification of Max binding protein as a novel binding protein of Nck1 and characterization of its role in inhibiting human liver cancer SK-HEP-1 cells.Chin Med J (Engl). 2012 Sep;125(18):3336-9.
• [15] Qualification of a select one-stage activated partial thromboplastin time-based clotting assay and two chromogenic assays for the post-administration monitoring of nonacog beta pegol.J Thromb Haemost. 2017 Oct;15(10):1901-1912. doi: 10.1111/jth.13787. Epub 2017 Sep 11.
• [16] Keratinocyte-derived laminin-332 protein promotes melanin synthesis via regulation of tyrosine uptake.J Biol Chem. 2014 Aug 1;289(31):21751-9. doi: 10.1074/jbc.M113.541177. Epub 2014 Jun 20.
• [17] A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage.Sci Rep. 2017 Aug 22;7(1):9126. doi: 10.1038/s41598-017-09070-y.
• [18] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [19] 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.
• [20] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [21] 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.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [24] 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.
• [25] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [26] 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.
• [27] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [28] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [33] 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.
• [34] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [35] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.