Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPT2I7B)

• DOT Name: Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8)
• Synonyms: Glucose transporter type 8; GLUT-8; Glucose transporter type X1
• Gene Name: SLC2A8
• UniProt ID: SL2A8_HUMAN
• Pfam ID: PF00083
• Sequence:
  MTPEDPEETQPLLGPPGGSAPRGRRVFLAAFAAALGPLSFGFALGYSSPAIPSLQRAAPP
  APRLDDAAASWFGAVVTLGAAAGGVLGGWLVDRAGRKLSLLLCSVPFVAGFAVITAAQDV
  WMLLGGRLLTGLACGVASLVAPVYISEIAYPAVRGLLGSCVQLMVVVGILLAYLAGWVLE
  WRWLAVLGCVPPSLMLLLMCFMPETPRFLLTQHRRQEAMAALRFLWGSEQGWEDPPIGAE
  QSFHLALLRQPGIYKPFIIGVSLMAFQQLSGVNAVMFYAETIFEEAKFKDSSLASVVVGV
  IQVLFTAVAALIMDRAGRRLLLVLSGVVMVFSTSAFGAYFKLTQGGPGNSSHVAISAPVS
  AQPVDASVGLAWLAVGSMCLFIAGFAVGWGPIPWLLMSEIFPLHVKGVATGICVLTNWLM
  AFLVTKEFSSLMEVLRPYGAFWLASAFCIFSVLFTLFCVPETKGKTLEQITAHFEGR
• Function: Insulin-regulated facilitative hexose transporter that mediates the transport of glucose and fructose. Facilitates hepatic influx of dietary trehalose, which in turn inhibits glucose and fructose influx triggering a starvation signal and hepatic autophagy through activation of AMPK and ULK1. Also able to mediate the transport of dehydroascorbate.
• Tissue Specificity: Highly expressed in testis, but not in testicular carcinoma. Lower amounts present in most other tissues.
• Reactome Pathway:
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[9]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Solute carrier family 2, facilitated glucose transporter member 8 (SLC2A8).	[10]

References

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• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] 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] 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.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [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] 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.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] 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.