Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE6F9U6)

• DOT Name: Solute carrier family 23 member 1 (SLC23A1)
• Synonyms: Na(+)/L-ascorbic acid transporter 1; Sodium-dependent vitamin C transporter 1; hSVCT1; Yolk sac permease-like molecule 3
• Gene Name: SLC23A1
• UniProt ID: S23A1_HUMAN
• Pfam ID: PF00860
• Sequence:
  MRAQEDLEGRTQHETTRDPSTPLPTEPKFDMLYKIEDVPPWYLCILLGFQHYLTCFSGTI
  AVPFLLAEALCVGHDQHMVSQLIGTIFTCVGITTLIQTTVGIRLPLFQASAFAFLVPAKA
  ILALERWKCPPEEEIYGNWSLPLNTSHIWHPRIREVQGAIMVSSVVEVVIGLLGLPGALL
  NYIGPLTVTPTVSLIGLSVFQAAGDRAGSHWGISACSILLIILFSQYLRNLTFLLPVYRW
  GKGLTLLRIQIFKMFPIMLAIMTVWLLCYVLTLTDVLPTDPKAYGFQARTDARGDIMAIA
  PWIRIPYPCQWGLPTVTAAAVLGMFSATLAGIIESIGDYYACARLAGAPPPPVHAINRGI
  FTEGICCIIAGLLGTGNGSTSSSPNIGVLGITKVGSRRVVQYGAAIMLVLGTIGKFTALF
  ASLPDPILGGMFCTLFGMITAVGLSNLQFVDMNSSRNLFVLGFSMFFGLTLPNYLESNPG
  AINTGILEVDQILIVLLTTEMFVGGCLAFILDNTVPGSPEERGLIQWKAGAHANSDMSSS
  LKSYDFPIGMGIVKRITFLKYIPICPVFKGFSSSSKDQIAIPEDTPENTETASVCTKV
• Function: Sodium:ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate. Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber ; [Isoform 2]: Inactive transporter.
• Tissue Specificity: Highly expressed in adult small intestine, kidney, thymus, ovary, colon, prostate and liver, and in fetal kidney, liver and thymus.
• KEGG Pathway: Vitamin digestion and absorption (hsa04977)
• Reactome Pathway: Vitamin C (ascorbate) metabolism (R-HSA-196836)

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Solute carrier family 23 member 1 (SLC23A1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[5]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Solute carrier family 23 member 1 (SLC23A1).	[6]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of Solute carrier family 23 member 1 (SLC23A1).	[7]
Taurocholic acid	DM2LZ8F	Phase 1/2	Taurocholic acid increases the expression of Solute carrier family 23 member 1 (SLC23A1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Solute carrier family 23 member 1 (SLC23A1).	[10]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Solute carrier family 23 member 1 (SLC23A1).	[7]

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] 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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Promoter analysis of the human ascorbic acid transporters SVCT1 and 2: mechanisms of adaptive regulation in liver epithelial cells. J Nutr Biochem. 2011 Apr;22(4):344-50. doi: 10.1016/j.jnutbio.2010.03.001. Epub 2010 May 14.
• [7] Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy. Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
• [8] 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.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.