Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3L6F7U)

• DOT Name: Mitochondrial fission process protein 1 (MTFP1)
• Synonyms: Mitochondrial 18 kDa protein; MTP18
• Gene Name: MTFP1
• Related Disease:
  Neoplasm
  Hepatocellular carcinoma
  Squamous cell carcinoma
• UniProt ID: MTFP1_HUMAN
• Pfam ID: PF10558
• Sequence:
  MSEPQPRGAERDLYRDTWVRYLGYANEVGEAFRSLVPAAVVWLSYGVASSYVLADAIDKG
  KKAGEVPSPEAGRSARVTVAVVDTFVWQALASVAIPGFTINRVCAASLYVLGTATRWPLA
  VRKWTTTALGLLTIPIIIHPIDRSVDFLLDSSLRKLYPTVGKPSSS
• Function: Involved in the mitochondrial division probably by regulating membrane fission. Loss-of-function induces the release of cytochrome c, which activates the caspase cascade and leads to apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[1]

16 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 process protein 1 (MTFP1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[10]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[5]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[5]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitochondrial fission process protein 1 (MTFP1).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial fission process protein 1 (MTFP1).	[16]

1 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 Mitochondrial fission process protein 1 (MTFP1).	[8]

References

• [1] MTFP1 overexpression promotes the growth of oral squamous cell carcinoma by inducing ROS production.Cell Biol Int. 2020 Mar;44(3):821-829. doi: 10.1002/cbin.11278. Epub 2019 Dec 19.
• [2] MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma.Cell Death Dis. 2018 Sep 20;9(10):956. doi: 10.1038/s41419-018-0987-x.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] 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.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] 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.
• [15] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.