Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0ZR03H)

• DOT Name: Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51)
• Synonyms: Mitochondrial NAD(+) transporter SLC25A51; Mitochondrial carrier triple repeat protein 1; Solute carrier family 25 member 51
• Gene Name: SLC25A51
• Related Disease: Hepatocellular carcinoma
• UniProt ID: S2551_HUMAN
• Pfam ID: PF00153
• Sequence:
  MMDSEAHEKRPPILTSSKQDISPHITNVGEMKHYLCGCCAAFNNVAITFPIQKVLFRQQL
  YGIKTRDAILQLRRDGFRNLYRGILPPLMQKTTTLALMFGLYEDLSCLLHKHVSAPEFAT
  SGVAAVLAGTTEAIFTPLERVQTLLQDHKHHDKFTNTYQAFKALKCHGIGEYYRGLVPIL
  FRNGLSNVLFFGLRGPIKEHLPTATTHSAHLVNDFICGGLLGAMLGFLFFPINVVKTRIQ
  SQIGGEFQSFPKVFQKIWLERDRKLINLFRGAHLNYHRSLISWGIINATYEFLLKVI
• Function: Mitochondrial membrane carrier protein that mediates the import of NAD(+) into mitochondria. Mitochondrial NAD(+) is required for glycolysis and mitochondrial respiration. Compared to SLC25A52, SLC25A51-mediated transport is essential for the import of NAD(+) in mitochondria. The transport mechanism, uniport or antiport, its electrogenicity and substrate selectivity, remain to be elucidated.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]

1 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 nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[2]

10 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 nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51 (SLC25A51).	[12]

References

• [1] Identification of tumor-associated antigens in human hepatocellular carcinoma by autoantibodies.Oncol Rep. 2008 Oct;20(4):979-85.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] 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.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.