Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5U4CFD)

• DOT Name: Sodium-dependent phosphate transport protein 3 (SLC17A2)
• Synonyms: Na(+)/PI cotransporter 3; Sodium/phosphate cotransporter 3; Solute carrier family 17 member 2
• Gene Name: SLC17A2
• UniProt ID: NPT3_HUMAN
• Pfam ID: PF07690
• Sequence:
  MDGKPATRKGPDFCSLRYGLALIMHFSNFTMITQRVSLSIAIIAMVNTTQQQGLSNASTE
  GPVADAFNNSSISIKEFDTKASVYQWSPETQGIIFSSINYGIILTLIPSGYLAGIFGAKK
  MLGAGLLISSLLTLFTPLAADFGVILVIMVRTVQGMAQGMAWTGQFTIWAKWAPPLERSK
  LTTIAGSGSAFGSFIILCVGGLISQALSWPFIFYIFGSTGCVCCLLWFTVIYDDPMHHPC
  ISVREKEHILSSLAQQPSSPGRAVPIKAMVTCLPLWAIFLGFFSHFWLCTIILTYLPTYI
  STLLHVNIRDSGVLSSLPFIAAASCTILGGQLADFLLSRNLLRLITVRKLFSSLGLLLPS
  ICAVALPFVASSYVITIILLILIPGTSNLCDSGFIINTLDIAPRYASFLMGISRGFGLIA
  GIISSTATGFLISQVGPVY
• Function: Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions. Mediates chloride-dependent transport of urate. Can actively transport inorganic phosphate into cells via Na(+) cotransport.
• Tissue Specificity: Expressed in the small intestine, kidney, spleen and testis. Not detected in fetal brain, bone marrow, and mammary gland.

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 Sodium-dependent phosphate transport protein 3 (SLC17A2).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[10]

15 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 Sodium-dependent phosphate transport protein 3 (SLC17A2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[6]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[8]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[9]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[9]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[11]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Sodium-dependent phosphate transport protein 3 (SLC17A2).	[12]

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] 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] 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] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [7] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [12] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.