Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSAD4EQ)

• DOT Name: Solute carrier family 35 member F2 (SLC35F2)
• Gene Name: SLC35F2
• Related Disease:
  Neoplasm
  Non-small-cell lung cancer
  Squamous cell carcinoma
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: S35F2_HUMAN
• Pfam ID: PF06027
• Sequence:
  MEADSPAGPGAPEPLAEGAAAEFSSLLRRIKGKLFTWNILKTIALGQMLSLCICGTAITS
  QYLAERYKVNTPMLQSFINYCLLFLIYTVMLAFRSGSDNLLVILKRKWWKYILLGLADVE
  ANYVIVRAYQYTTLTSVQLLDCFGIPVLMALSWFILHARYRVIHFIAVAVCLLGVGTMVG
  ADILAGREDNSGSDVLIGDILVLLGASLYAISNVCEEYIVKKLSRQEFLGMVGLFGTIIS
  GIQLLIVEYKDIASIHWDWKIALLFVAFALCMFCLYSFMPLVIKVTSATSVNLGILTADL
  YSLFVGLFLFGYKFSGLYILSFTVIMVGFILYCSTPTRTAEPAESSVPPVTSIGIDNLGL
  KLEENLQETHSAVL
• Function: Putative solute transporter.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[1]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[3]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[3]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[3]

17 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 35 member F2 (SLC35F2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Solute carrier family 35 member F2 (SLC35F2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[13]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Solute carrier family 35 member F2 (SLC35F2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[20]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Solute carrier family 35 member F2 (SLC35F2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Solute carrier family 35 member F2 (SLC35F2).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Solute carrier family 35 member F2 (SLC35F2).	[18]

References

• [1] Knockdown of SLC35F2 Inhibits the Proliferation and Metastasis of Bladder Cancer Cells.Onco Targets Ther. 2019 Dec 10;12:10771-10786. doi: 10.2147/OTT.S229332. eCollection 2019.
• [2] Highly expressed SLC35F2 in non-small cell lung cancer is associated with pathological staging.Mol Med Rep. 2011 Nov-Dec;4(6):1289-93. doi: 10.3892/mmr.2011.572. Epub 2011 Aug 24.
• [3] Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor- type I receptor/apoptosis signal-regulating kinase 1/mitogen-activated protein kinase signaling axis.Cancer Sci. 2018 Mar;109(3):642-655. doi: 10.1111/cas.13478. Epub 2018 Feb 1.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [18] 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.
• [19] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] 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.