Details of Drug Off-Target (DOT)

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

• DOT Name: Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6)
• Synonyms: Glucose transporter type 6; GLUT-6
• Gene Name: SLC2A6
• Related Disease: Cardiomyopathy
• UniProt ID: GTR6_HUMAN
• Pfam ID: PF00083
• Sequence:
  MQEPLLGAEGPDYDTFPEKPPPSPGDRARVGTLQNKRVFLATFAAVLGNFSFGYALVYTS
  PVIPALERSLDPDLHLTKSQASWFGSVFTLGAAAGGLSAMILNDLLGRKLSIMFSAVPSA
  AGYALMAGAHGLWMLLLGRTLTGFAGGLTAACIPVYVSEIAPPGVRGALGATPQLMAVFG
  SLSLYALGLLLPWRWLAVAGEAPVLIMILLLSFMPNSPRFLLSRGRDEEALRALAWLRGT
  DVDVHWEFEQIQDNVRRQSSRVSWAEARAPHVCRPITVALLMRLLQQLTGITPILVYLQS
  IFDSTAVLLPPKDDAAIVGAVRLLSVLIAALTMDLAGRKVLLFVSAAIMFAANLTLGLYI
  HFGPRPLSPNSTAGLESESWGDLAQPLAAPAGYLTLVPLLATMLFIMGYAVGWGPITWLL
  MSEVLPLRARGVASGLCVLASWLTAFVLTKSFLPVVSTFGLQVPFFFFAAICLVSLVFTG
  CCVPETKGRSLEQIESFFRTGRRSFLR
• Function: Probable sugar transporter that acts as a regulator of glycolysis in macrophages (Probable). Does not transport glucose.
• Tissue Specificity: Highly expressed in brain, spleen and peripheral blood leukocytes.
• Reactome Pathway: Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Limited	Autosomal dominant	[1]

2 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 2, facilitated glucose transporter member 6 (SLC2A6).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[13]

14 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 2, facilitated glucose transporter member 6 (SLC2A6).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[7]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[8]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[8]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6).	[16]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] 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.
• [5] 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.
• [6] 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.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115100. doi: 10.1016/j.taap.2020.115100. Epub 2020 Jun 6.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] 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.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.