Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG0B7RM)

• DOT Name: Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23)
• Synonyms: Mitochondrial ATP-Mg/Pi carrier protein 2; Short calcium-binding mitochondrial carrier protein 3; SCaMC-3; Solute carrier family 25 member 23
• Gene Name: SLC25A23
• UniProt ID: SCMC3_HUMAN
• Pfam ID: PF13499 ; PF00153
• Sequence:
  MRGSPGDAERRQRWGRLFEELDSNKDGRVDVHELRQGLARLGGGNPDPGAQQGISSEGDA
  DPDGGLDLEEFSRYLQEREQRLLLMFHSLDRNQDGHIDVSEIQQSFRALGISISLEQAEK
  ILHSMDRDGTMTIDWQEWRDHFLLHSLENVEDVLYFWKHSTVLDIGECLTVPDEFSKQEK
  LTGMWWKQLVAGAVAGAVSRTGTAPLDRLKVFMQVHASKTNRLNILGGLRSMVLEGGIRS
  LWRGNGINVLKIAPESAIKFMAYEQIKRAILGQQETLHVQERFVAGSLAGATAQTIIYPM
  EVLKTRLTLRRTGQYKGLLDCARRILEREGPRAFYRGYLPNVLGIIPYAGIDLAVYETLK
  NWWLQQYSHDSADPGILVLLACGTISSTCGQIASYPLALVRTRMQAQASIEGGPQLSMLG
  LLRHILSQEGMRGLYRGIAPNFMKVIPAVSISYVVYENMKQALGVTSR
• Function: Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenine nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenine nucleotide-dependent metabolic pathways. Also acts as a regulator of mitochondrial calcium uptake and can probably transport trace amounts of other divalent metal cations in complex with ATP. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides.
• Tissue Specificity: Expressed at low levels in most tissues examined, with highest expression in brain, skeletal muscle and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

13 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 adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[8]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[9]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Mitochondrial adenyl nucleotide antiporter SLC25A23 (SLC25A23).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] 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.
• [8] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [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] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] 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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.