Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM6UWNH)

• DOT Name: Sideroflexin-3 (SFXN3)
• Gene Name: SFXN3
• UniProt ID: SFXN3_HUMAN
• Pfam ID: PF03820
• Sequence:
  MGELPLDINIQEPRWDQSTFLGRARHFFTVTDPRNLLLSGAQLEASRNIVQNYRAGVVTP
  GITEDQLWRAKYVYDSAFHPDTGEKVVLIGRMSAQVPMNMTITGCMLTFYRKTPTVVFWQ
  WVNQSFNAIVNYSNRSGDTPITVRQLGTAYVSATTGAVATALGLKSLTKHLPPLVGRFVP
  FAAVAAANCINIPLMRQRELQVGIPVADEAGQRLGYSVTAAKQGIFQVVISRICMAIPAM
  AIPPLIMDTLEKKDFLKRRPWLGAPLQVGLVGFCLVFATPLCCALFPQKSSIHISNLEPE
  LRAQIHEQNPSVEVVYYNKGL
• Function: Mitochondrial serine transporter that mediates transport of serine into mitochondria, an important step of the one-carbon metabolism pathway. Mitochondrial serine is converted to glycine and formate, which then exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors.

Molecular Interaction Atlas (MIA) of This DOT

17 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 Sideroflexin-3 (SFXN3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sideroflexin-3 (SFXN3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sideroflexin-3 (SFXN3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sideroflexin-3 (SFXN3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sideroflexin-3 (SFXN3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sideroflexin-3 (SFXN3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sideroflexin-3 (SFXN3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Sideroflexin-3 (SFXN3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sideroflexin-3 (SFXN3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sideroflexin-3 (SFXN3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sideroflexin-3 (SFXN3).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Sideroflexin-3 (SFXN3).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Sideroflexin-3 (SFXN3).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sideroflexin-3 (SFXN3).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Sideroflexin-3 (SFXN3).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sideroflexin-3 (SFXN3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Sideroflexin-3 (SFXN3).	[19]

2 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 affects the methylation of Sideroflexin-3 (SFXN3).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Sideroflexin-3 (SFXN3).	[18]

References

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• [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] 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.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] 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.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] 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.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] 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.
• [15] 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.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] 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.
• [19] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.