Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSXZ356)

• DOT Name: Myelin expression factor 2 (MYEF2)
• Synonyms: MEF-2; MyEF-2; MST156
• Gene Name: MYEF2
• Related Disease:
  Advanced cancer
  Familial dilated cardiomyopathy
• UniProt ID: MYEF2_HUMAN
• Pfam ID: PF00076
• Sequence:
  MADANKAEVPGATGGDSPHLQPAEPPGEPRREPHPAEAEKQQPQHSSSSNGVKMENDESA
  KEEKSDLKEKSTGSKKANRFHPYSKDKNSGAGEKKGPNRNRVFISNIPYDMKWQAIKDLM
  REKVGEVTYVELFKDAEGKSRGCGVVEFKDEEFVKKALETMNKYDLSGRPLNIKEDPDGE
  NARRALQRTGGSFPGGHVPDMGSGLMNLPPSILNNPNIPPEVISNLQAGRLGSTIFVANL
  DFKVGWKKLKEVFSIAGTVKRADIKEDKDGKSRGMGTVTFEQAIEAVQAISMFNGQFLFD
  RPMHVKMDDKSVPHEEYRSHDGKTPQLPRGLGGIGMGLGPGGQPISASQLNIGGVMGNLG
  PGGMGMDGPGFGGMNRIGGGIGFGGLEAMNSMGGFGGVGRMGELYRGAMTSSMERDFGRG
  DIGINQGFGDSFGRLGSAMIGGFAGRIGSSNMGPVGSGISGGMGSMNSVTGGMGMGLDRM
  SSSFDRMGPGIGAILERSIDMDRGFLSGPMGSGMRERIGSKGNQIFVRNLPFDLTWQKLK
  EKFSQCGHVMFAEIKMENGKSKGCGTVRFDSPESAEKACRIMNGIKISGREIDVRLDRNA
• Function: Transcriptional repressor of the myelin basic protein gene (MBP). Binds to the proximal MB1 element 5'-TTGTCC-3' of the MBP promoter. Its binding to MB1 and function are inhibited by PURA.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Familial dilated cardiomyopathy	DISBHDU9	Strong	Genetic Variation	[2]

12 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 Myelin expression factor 2 (MYEF2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Myelin expression factor 2 (MYEF2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myelin expression factor 2 (MYEF2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myelin expression factor 2 (MYEF2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myelin expression factor 2 (MYEF2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Myelin expression factor 2 (MYEF2).	[8]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Myelin expression factor 2 (MYEF2).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Myelin expression factor 2 (MYEF2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myelin expression factor 2 (MYEF2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myelin expression factor 2 (MYEF2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Myelin expression factor 2 (MYEF2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Myelin expression factor 2 (MYEF2).	[14]

References

• [1] MEF-2 isoforms' (A-D) roles in development and tumorigenesis.Oncotarget. 2019 Apr 12;10(28):2755-2787. doi: 10.18632/oncotarget.26763. eCollection 2019 Apr 12.
• [2] Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32.Circulation. 1995 Dec 15;92(12):3387-9. doi: 10.1161/01.cir.92.12.3387.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] 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.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.