Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLOR68D)

• DOT Name: Mitochondrial fission regulator 2 (MTFR2)
• Synonyms: DUF729 domain-containing protein 1
• Gene Name: MTFR2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Glioblastoma multiforme
• UniProt ID: MTFR2_HUMAN
• Pfam ID: PF05308
• Sequence:
  MSLILNILREMLEYFGVPVEQVLLIWENKDYGSTRSIVRIIGKMLPLEPCRRPNFELIPL
  LNSVDSDNCGSMVPSFADILYVANDEEASYLRFRNSIWKNEEEKVEIFHPLRLVRDPLSP
  AVRQKETVKNDLPVNEAAIRKIAALENELTFLRSQIAAIVEMQELKNSTNSSSFGLSDER
  ISLGQLSSSRAAHLSVDPDQLPGSVLSPPPPPPLPPQFSSLQPPCFPPVQPGSNNICDSD
  NPATEMSKQNPAANKTNYSHHSKSQRNKDIPNMLDVLKDMNKVKLRAIERSPGGRPIHKR
  KRQNSHWDPVSLISHALKQKFAFQEDDSFEKENRSWESSPFSSPETSRFGHHISQSEGQR
  TKEEMVNTKAVDQGISNTSLLNSRI
• Function: May play a role in mitochondrial aerobic respiration essentially in the testis. Can also promote mitochondrial fission.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Mitochondrial fission regulator 2 (MTFR2).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Mitochondrial fission regulator 2 (MTFR2).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Mitochondrial fission regulator 2 (MTFR2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[13]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[14]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[15]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[17]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial fission regulator 2 (MTFR2).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial fission regulator 2 (MTFR2).	[24]

References

• [1] Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells.Aging (Albany NY). 2019 Nov 18;11(22):10203-10219. doi: 10.18632/aging.102442. Epub 2019 Nov 18.
• [2] Targeting dual specificity protein kinase TTK attenuates tumorigenesis of glioblastoma.Oncotarget. 2017 Dec 11;9(3):3081-3088. doi: 10.18632/oncotarget.23152. eCollection 2018 Jan 9.
• [3] 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.
• [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] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [15] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [16] Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.