Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIA6YUG)

• DOT Name: MyoD family inhibitor (MDFI)
• Synonyms: Myogenic repressor I-mf
• Gene Name: MDFI
• Related Disease:
  Colorectal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Asthma
• UniProt ID: MDFI_HUMAN
• Pfam ID: PF15316
• Sequence:
  MYQVSGQRPSGCDAPYGAPSAAPGPAQTLSLLPGLEVVTGSTHPAEAAPEEGSLEEAATP
  MPQGNGPGIPQGLDSTDLDVPTEAVTCQPQGNPLGCTPLLPNDSGHPSELGGTRRAGNGA
  LGGPKAHRKLQTHPSLASQGSKKSKSSSKSTTSQIPLQAQEDCCVHCILSCLFCEFLTLC
  NIVLDCATCGSCSSEDSCLCCCCCGSGECADCDLPCDLDCGILDACCESADCLEICMECC
  GLCFSS
• Function: Inhibits the transactivation activity of the Myod family of myogenic factors and represses myogenesis. Acts by associating with Myod family members and retaining them in the cytoplasm by masking their nuclear localization signals. Can also interfere with the DNA-binding activity of Myod family members. Plays an important role in trophoblast and chondrogenic differentiation. Regulates the transcriptional activity of TCF7L1/TCF3 by interacting directly with TCF7L1/TCF3 and preventing it from binding DNA. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[3]
Asthma	DISW9QNS	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of MyoD family inhibitor (MDFI).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of MyoD family inhibitor (MDFI).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of MyoD family inhibitor (MDFI).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MyoD family inhibitor (MDFI).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of MyoD family inhibitor (MDFI).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of MyoD family inhibitor (MDFI).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MyoD family inhibitor (MDFI).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MyoD family inhibitor (MDFI).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of MyoD family inhibitor (MDFI).	[13]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of MyoD family inhibitor (MDFI).	[14]

References

• [1] DNA methylation of CMTM3, SSTR2, and MDFI genes in colorectal cancer.Gene. 2017 Sep 30;630:1-7. doi: 10.1016/j.gene.2017.07.082. Epub 2017 Aug 4.
• [2] I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions.Virology. 2015 Dec;486:219-27. doi: 10.1016/j.virol.2015.09.020. Epub 2015 Oct 27.
• [3] Hypermethylation of MDFI promoter with NSCLC is specific for females, non-smokers and people younger than 65.Oncol Lett. 2018 Jun;15(6):9017-9024. doi: 10.3892/ol.2018.8535. Epub 2018 Apr 18.
• [4] Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment.Allergol Int. 2018 Apr;67(2):253-258. doi: 10.1016/j.alit.2017.09.004. Epub 2017 Oct 21.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] 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.
• [8] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] 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.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.
• [13] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [14] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.