Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0EDNV9)

• DOT Name: Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12)
• Synonyms: Glucose transporter type 12; GLUT-12
• Gene Name: SLC2A12
• UniProt ID: GTR12_HUMAN
• Pfam ID: PF00083
• Sequence:
  MVPVENTEGPSLLNQKGTAVETEGSGSRHPPWARGCGMFTFLSSVTAAVSGLLVGYELGI
  ISGALLQIKTLLALSCHEQEMVVSSLVIGALLASLTGGVLIDRYGRRTAIILSSCLLGLG
  SLVLILSLSYTVLIVGRIAIGVSISLSSIATCVYIAEIAPQHRRGLLVSLNELMIVIGIL
  SAYISNYAFANVFHGWKYMFGLVIPLGVLQAIAMYFLPPSPRFLVMKGQEGAASKVLGRL
  RALSDTTEELTVIKSSLKDEYQYSFWDLFRSKDNMRTRIMIGLTLVFFVQITGQPNILFY
  ASTVLKSVGFQSNEAASLASTGVGVVKVISTIPATLLVDHVGSKTFLCIGSSVMAASLVT
  MGIVNLNIHMNFTHICRSHNSINQSLDESVIYGPGNLSTNNNTLRDHFKGISSHSRSSLM
  PLRNDVDKRGETTSASLLNAGLSHTEYQIVTDPGDVPAFLKWLSLASLLVYVAAFSIGLG
  PMPWLVLSEIFPGGIRGRAMALTSSMNWGINLLISLTFLTVTDLIGLPWVCFIYTIMSLA
  SLLFVVMFIPETKGCSLEQISMELAKVNYVKNNICFMSHHQEELVPKQPQKRKPQEQLLE
  CNKLCGRGQSRQLSPET
• Function: Insulin-independent facilitative glucose transporter.
• Tissue Specificity: Predominantly expressed in skeletal muscle, heart and prostate, with lower levels in brain, placenta and kidney.
• Reactome Pathway: Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DOT

16 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 Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[10]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the methylation of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Solute carrier family 2, facilitated glucose transporter member 12 (SLC2A12).	[16]

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] 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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [10] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [11] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Reduced camptothecin sensitivity of estrogen receptor-positive human breast cancer cells following exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with DNA methylation changes. Environ Toxicol. 2019 Apr;34(4):401-414.
• [14] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [15] 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.
• [16] 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.