Details of Drug Off-Target (DOT)

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

• DOT Name: Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25)
• Synonyms: Mitochondrial ATP-Mg/Pi carrier protein 3; Mitochondrial Ca(2+)-dependent solute carrier protein 3; Short calcium-binding mitochondrial carrier protein 2; SCaMC-2; Solute carrier family 25 member 25
• Gene Name: SLC25A25
• UniProt ID: SCMC2_HUMAN
• Pfam ID: PF13499 ; PF13833 ; PF00153
• Sequence:
  MLCLCLYVPVIGEAQTEFQYFESKGLPAELKSIFKLSVFIPSQEFSTYRQWKQKIVQAGD
  KDLDGQLDFEEFVHYLQDHEKKLRLVFKSLDKKNDGRIDAQEIMQSLRDLGVKISEQQAE
  KILKSMDKNGTMTIDWNEWRDYHLLHPVENIPEIILYWKHSTIFDVGENLTVPDEFTVEE
  RQTGMWWRHLVAGGGAGAVSRTCTAPLDRLKVLMQVHASRSNNMGIVGGFTQMIREGGAR
  SLWRGNGINVLKIAPESAIKFMAYEQIKRLVGSDQETLRIHERLVAGSLAGAIAQSSIYP
  MEVLKTRMALRKTGQYSGMLDCARRILAREGVAAFYKGYVPNMLGIIPYAGIDLAVYETL
  KNAWLQHYAVNSADPGVFVLLACGTMSSTCGQLASYPLALVRTRMQAQASIEGAPEVTMS
  SLFKHILRTEGAFGLYRGLAPNFMKVIPAVSISYVVYENLKITLGVQSR
• Function: Electroneutral antiporter that most probably mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it could have a broader specificity for adenyl nucleotides. By regulating the mitochondrial matrix adenyl nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways.
• Tissue Specificity: Widely expressed. Expressed in fetal and adult liver, skeletal muscle, testis, ovary, hippocampus and caudate nucleus.; [Isoform 1]: Expressed in all tissues tested.; [Isoform 2]: Expression is restricted to kidney and lung.

Molecular Interaction Atlas (MIA) of This DOT

2 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 adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[4]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25).	[14]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.