Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4U88UP)

• DOT Name: Max dimerization protein 3 (MXD3)
• Synonyms: Max dimerizer 3; Class C basic helix-loop-helix protein 13; bHLHc13; Max-associated protein 3; Max-interacting transcriptional repressor MAD3; Myx
• Gene Name: MXD3
• Related Disease:
  Cerebellar neoplasm
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Advanced cancer
  Brain neoplasm
  Cardiovascular disease
  Craniosynostosis
  Glioblastoma multiforme
  Neuroblastoma
  Medulloblastoma
• UniProt ID: MAD3_HUMAN
• Pfam ID: PF00010
• Sequence:
  MEPLASNIQVLLQAAEFLERREREAEHGYASLCPHRSPGPIHRRKKRPPQAPGAQDSGRS
  VHNELEKRRRAQLKRCLERLKQQMPLGADCARYTTLSLLRRARMHIQKLEDQEQRARQLK
  ERLRSKQQSLQRQLEQLRGLAGAAERERLRADSLDSSGLSSERSDSDQEELEVDVESLVF
  GGEAELLRGFVAGQEHSYSHGGGAWL
• Function: Transcriptional repressor. Binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. Antagonizes MYC transcriptional activity by competing for MAX and suppresses MYC dependent cell transformation.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar neoplasm	DIS859E0	Definitive	Altered Expression	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[4]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[5]
Craniosynostosis	DIS6J405	Strong	Altered Expression	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[7]
Medulloblastoma	DISZD2ZL	Limited	Altered Expression	[3]

11 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 dimerization protein 3 (MXD3).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Max dimerization protein 3 (MXD3).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Max dimerization protein 3 (MXD3).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Max dimerization protein 3 (MXD3).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Max dimerization protein 3 (MXD3).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Max dimerization protein 3 (MXD3).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Max dimerization protein 3 (MXD3).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Max dimerization protein 3 (MXD3).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Max dimerization protein 3 (MXD3).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Max dimerization protein 3 (MXD3).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Max dimerization protein 3 (MXD3).	[18]

1 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 increases the methylation of Max dimerization protein 3 (MXD3).	[17]

References

• [1] A novel role of the Mad family member Mad3 in cerebellar granule neuron precursor proliferation.Mol Cell Biol. 2007 Dec;27(23):8178-89. doi: 10.1128/MCB.00656-06. Epub 2007 Sep 24.
• [2] Targeted therapy with MXD3 siRNA, anti-CD22 antibody and nanoparticles for precursor B-cell acute lymphoblastic leukaemia.Br J Haematol. 2014 Nov;167(4):487-99. doi: 10.1111/bjh.13066. Epub 2014 Sep 8.
• [3] Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma.Front Mol Biosci. 2019 Feb 19;6:5. doi: 10.3389/fmolb.2019.00005. eCollection 2019.
• [4] From cerebellar proliferation to tumorigenesis: new insights into the role of Mad3.Cell Cycle. 2008 Feb 15;7(4):423-7. doi: 10.4161/cc.7.4.5413. Epub 2007 Dec 6.
• [5] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [6] Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome.Am J Transl Res. 2017 Feb 15;9(2):214-229. eCollection 2017.
• [7] MXD3 antisense oligonucleotide with superparamagnetic iron oxide nanoparticles: A new targeted approach for neuroblastoma.Nanomedicine. 2020 Feb;24:102127. doi: 10.1016/j.nano.2019.102127. Epub 2019 Nov 26.
• [8] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] 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.
• [12] 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.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [15] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [16] Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005 Feb;4(2):233-41.
• [17] 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.
• [18] 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.