Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU3B4WU)

• DOT Name: Myeloid leukemia factor 2 (MLF2)
• Synonyms: Myelodysplasia-myeloid leukemia factor 2
• Gene Name: MLF2
• Related Disease:
  Acute leukaemia
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: MLF2_HUMAN
• Pfam ID: PF10248
• Sequence:
  MFRFMRDVEPEDPMFLMDPFAIHRQHMSRMLSGGFGYSPFLSITDGNMPGTRPASRRMQQ
  AGAVSPFGMLGMSGGFMDMFGMMNDMIGNMEHMTAGGNCQTFSSSTVISYSNTGDGAPKV
  YQETSEMRSAPGGIRETRRTVRDSDSGLEQMSIGHHIRDRAHILQRSRNHRTGDQEERQD
  YINLDESEAAAFDDEWRRETSRFRQQRPLEFRRLESSGAGGRRAEGPPRLAIQGPEDSPS
  RQSRRYDW
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Myeloid leukemia factor 2 (MLF2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Myeloid leukemia factor 2 (MLF2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Myeloid leukemia factor 2 (MLF2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Myeloid leukemia factor 2 (MLF2).	[7]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Myeloid leukemia factor 2 (MLF2).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Myeloid leukemia factor 2 (MLF2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Myeloid leukemia factor 2 (MLF2).	[11]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Myeloid leukemia factor 2 (MLF2).	[12]

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 Myeloid leukemia factor 2 (MLF2).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Myeloid leukemia factor 2 (MLF2).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myeloid leukemia factor 2 (MLF2).	[10]

References

• [1] cDNA cloning, tissue distribution, and chromosomal localization of myelodysplasia/myeloid leukemia factor 2 (MLF2).Genomics. 1996 Jul 15;35(2):392-6. doi: 10.1006/geno.1996.0376.
• [2] Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling.Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8838-43. doi: 10.1073/pnas.1320769111. Epub 2014 May 29.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.