Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VA5PI)

• DOT Name: Kidney mitochondrial carrier protein 1 (SLC25A30)
• Synonyms: Solute carrier family 25 member 30; Uncoupling protein 6
• Gene Name: SLC25A30
• UniProt ID: KMCP1_HUMAN
• Pfam ID: PF00153
• Sequence:
  MSALNWKPFVYGGLASITAECGTFPIDLTKTRLQIQGQTNDAKFKEIRYRGMLHALVRIG
  REEGLKALYSGIAPAMLRQASYGTIKIGTYQSLKRLFIERPEDETLPINVICGILSGVIS
  STIANPTDVLKIRMQAQSNTIQGGMIGNFMNIYQQEGTRGLWKGVSLTAQRAAIVVGVEL
  PVYDITKKHLILSGLMGDTVYTHFLSSFTCGLAGALASNPVDVVRTRMMNQRVLRDGRCS
  GYTGTLDCLLQTWKNEGFFALYKGFWPNWLRLGPWNIIFFVTYEQLKKLDL
• Function: Antiporter that transports inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate. The sulfate/sulfate exchange is much higher than the phosphate/phosphate and malate/malate exchanges. The transport affinities is higher for sulfate and thiosulfate than for any other substrate. May catalyze the export of sulfite and thiosulfate (the hydrogen sulfide degradation products) from the mitochondria, thereby modulating the level of the hydrogen sulfide (Probable). Also may mediate a very low unidirectional transport of sulfate, phosphate and (S)-malate.

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 Kidney mitochondrial carrier protein 1 (SLC25A30).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kidney mitochondrial carrier protein 1 (SLC25A30).	[14]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] 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.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.