Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLB1VFT)

• DOT Name: Mitochondrial fission regulator 1 (MTFR1)
• Synonyms: Chondrocyte protein with a poly-proline region
• Gene Name: MTFR1
• UniProt ID: MTFR1_HUMAN
• Pfam ID: PF05308
• Sequence:
  MLGWIKRLIRMVFQQVGVSMQSVLWSRKPYGSSRSIVRKIGTNLSLIQCPRVQFQINSHA
  TEWSPSHPGEDAVASFADVGWVAKEEGECSARLRTEVRSRPPLQDDLLFFEKAPSRQISL
  PDLSQEEPQLKTPALANEEALQKICALENELAALRAQIAKIVTQQEQQNLTAGDLDSTTF
  GTIPPHPPPPPPPLPPPALGLHQSTSAVDLIKERREKRANAGKTLVKNNPKKPEMPNMLE
  ILKEMNSVKLRSVKRSEQDVKPKPVDATDPAALIAEALKKKFAYRYRSDSQDEVEKGIPK
  SESEATSERVLFGPHMLKPTGKMKALIENVSDS
• Function: May play a role in mitochondrial aerobic respiration. May also regulate mitochondrial organization and fission.

Molecular Interaction Atlas (MIA) of This DOT

12 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 Mitochondrial fission regulator 1 (MTFR1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial fission regulator 1 (MTFR1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial fission regulator 1 (MTFR1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial fission regulator 1 (MTFR1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Mitochondrial fission regulator 1 (MTFR1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial fission regulator 1 (MTFR1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Mitochondrial fission regulator 1 (MTFR1).	[5]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Mitochondrial fission regulator 1 (MTFR1).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Mitochondrial fission regulator 1 (MTFR1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitochondrial fission regulator 1 (MTFR1).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Mitochondrial fission regulator 1 (MTFR1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitochondrial fission regulator 1 (MTFR1).	[12]

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 decreases the methylation of Mitochondrial fission regulator 1 (MTFR1).	[9]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.