Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ4F5LK)

• DOT Name: Thiosulfate sulfurtransferase (TST)
• Synonyms: EC 2.8.1.1; Rhodanese
• Gene Name: TST
• UniProt ID: THTR_HUMAN
• PDB ID: 8AGF; 8BGQ
• EC Number: 2.8.1.1
• Pfam ID: PF00581
• Sequence:
  MVHQVLYRALVSTKWLAESIRTGKLGPGLRVLDASWYSPGTREARKEYLERHVPGASFFD
  IEECRDTASPYEMMLPSEAGFAEYVGRLGISNHTHVVVYDGEHLGSFYAPRVWWMFRVFG
  HRTVSVLNGGFRNWLKEGHPVTSEPSRPEPAVFKATLDRSLLKTYEQVLENLESKRFQLV
  DSRSQGRFLGTEPEPDAVGLDSGHIRGAVNMPFMDFLTEDGFEKGPEELRALFQTKKVDL
  SQPLIATCRKGVTACHVALAAYLCGKPDVAVYDGSWSEWFRRAPPESRVSQGKSEKA
• Function: Formation of iron-sulfur complexes, cyanide detoxification or modification of sulfur-containing enzymes. Other thiol compounds, besides cyanide, can act as sulfur ion acceptors. Also has weak mercaptopyruvate sulfurtransferase (MST) activity. Together with MRPL18, acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Sulfur metabolism (hsa00920)
  Metabolic pathways (hsa01100)
  Sulfur relay system (hsa04122)
• Reactome Pathway:
  Degradation of cysteine and homocysteine (R-HSA-1614558)
  Sulfide oxidation to sulfate (R-HSA-1614517)
• BioCyc Pathway: MetaCyc:HS05179-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Thiosulfate sulfurtransferase (TST) affects the response to substance of Fluorouracil.	[19]
Topotecan	DMP6G8T	Approved	Thiosulfate sulfurtransferase (TST) affects the response to substance of Topotecan.	[20]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Thiosulfate sulfurtransferase (TST).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thiosulfate sulfurtransferase (TST).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Thiosulfate sulfurtransferase (TST).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thiosulfate sulfurtransferase (TST).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Thiosulfate sulfurtransferase (TST).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thiosulfate sulfurtransferase (TST).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Thiosulfate sulfurtransferase (TST).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Thiosulfate sulfurtransferase (TST).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Thiosulfate sulfurtransferase (TST).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Thiosulfate sulfurtransferase (TST).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Thiosulfate sulfurtransferase (TST).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Thiosulfate sulfurtransferase (TST).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Thiosulfate sulfurtransferase (TST).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Thiosulfate sulfurtransferase (TST).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Thiosulfate sulfurtransferase (TST).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Thiosulfate sulfurtransferase (TST).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thiosulfate sulfurtransferase (TST).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Thiosulfate sulfurtransferase (TST).	[17]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Thiosulfate sulfurtransferase (TST).	[18]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] 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.
• [18] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [19] Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Cancer Res. 2004 Nov 15;64(22):8167-76. doi: 10.1158/0008-5472.CAN-04-0970.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.