Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9F01S)

• DOT Name: Mitoferrin-1 (SLC25A37)
• Synonyms: Mitochondrial iron transporter 1; Mitochondrial solute carrier protein; Solute carrier family 25 member 37
• Gene Name: SLC25A37
• UniProt ID: MFRN1_HUMAN
• Pfam ID: PF00153
• Sequence:
  MELRSGSVGSQAVARRMDGDSRDGGGGKDATGSEDYENLPTSASVSTHMTAGAMAGILEH
  SVMYPVDSVKTRMQSLSPDPKAQYTSIYGALKKIMRTEGFWRPLRGVNVMIMGAGPAHAM
  YFACYENMKRTLNDVFHHQGNSHLANGIAGSMATLLHDAVMNPAEVVKQRLQMYNSQHRS
  AISCIRTVWRTEGLGAFYRSYTTQLTMNIPFQSIHFITYEFLQEQVNPHRTYNPQSHIIS
  GGLAGALAAAATTPLDVCKTLLNTQENVALSLANISGRLSGMANAFRTVYQLNGLAGYFK
  GIQARVIYQMPSTAISWSVYEFFKYFLTKRQLENRAPY
• Function: Mitochondrial iron transporter that specifically mediates iron uptake in developing erythroid cells, thereby playing an essential role in heme biosynthesis.
• Reactome Pathway: Mitochondrial iron-sulfur cluster biogenesis (R-HSA-1362409)

Molecular Interaction Atlas (MIA) of This DOT

15 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 Mitoferrin-1 (SLC25A37).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitoferrin-1 (SLC25A37).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mitoferrin-1 (SLC25A37).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitoferrin-1 (SLC25A37).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitoferrin-1 (SLC25A37).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Mitoferrin-1 (SLC25A37).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Mitoferrin-1 (SLC25A37).	[7]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Mitoferrin-1 (SLC25A37).	[8]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine increases the expression of Mitoferrin-1 (SLC25A37).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Mitoferrin-1 (SLC25A37).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Mitoferrin-1 (SLC25A37).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitoferrin-1 (SLC25A37).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitoferrin-1 (SLC25A37).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Mitoferrin-1 (SLC25A37).	[15]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Mitoferrin-1 (SLC25A37).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Mitoferrin-1 (SLC25A37).	[14]

References

• [1] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [9] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [10] 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.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [13] 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.
• [14] 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.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [16] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.