Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7EJ6LQ)

• DOT Name: Sulfotransferase 1A2 (SULT1A2)
• Synonyms: ST1A2; EC 2.8.2.1; Aryl sulfotransferase 2; Phenol sulfotransferase 2; Phenol-sulfating phenol sulfotransferase 2; P-PST 2
• Gene Name: SULT1A2
• UniProt ID: ST1A2_HUMAN
• PDB ID: 1Z29
• EC Number: 2.8.2.1
• Pfam ID: PF00685
• Sequence:
  MELIQDISRPPLEYVKGVPLIKYFAEALGPLQSFQARPDDLLISTYPKSGTTWVSQILDM
  IYQGGDLEKCHRAPIFMRVPFLEFKVPGIPSGMETLKNTPAPRLLKTHLPLALLPQTLLD
  QKVKVVYVARNAKDVAVSYYHFYHMAKVYPHPGTWESFLEKFMAGEVSYGSWYQHVQEWW
  ELSRTHPVLYLFYEDMKENPKREIQKILEFVGRSLPEETVDLMVEHTSFKEMKKNPMTNY
  TTVRREFMDHSISPFMRKGMAGDWKTTFTVAQNERFDADYAKKMAGCSLSFRSEL
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Is also responsible for the sulfonation and activation of minoxidil. Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.
• KEGG Pathway: Chemical carcinogenesis - D. adducts (hsa05204)
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)
• BioCyc Pathway: MetaCyc:HS11091-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Sulfotransferase 1A2 (SULT1A2) affects the response to substance of Cisplatin.	[15]
5-hydroxymethyl-2-furfural	DMPFVJB	Phase 2	Sulfotransferase 1A2 (SULT1A2) increases the activity of 5-hydroxymethyl-2-furfural.	[19]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	Sulfotransferase 1A2 (SULT1A2) increases the activity of 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE.	[20]
Nitrobenzanthrone	DMN6L70	Investigative	Sulfotransferase 1A2 (SULT1A2) increases the activity of Nitrobenzanthrone.	[21]

This DOT Affected the Biotransformations of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzyl alcohol	DMBVYDI	Approved	Sulfotransferase 1A2 (SULT1A2) increases the sulfation of Benzyl alcohol.	[16]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	Sulfotransferase 1A2 (SULT1A2) increases the sulfation of 3,4-Dihydroxycinnamic Acid.	[17]
Resveratrol	DM3RWXL	Phase 3	Sulfotransferase 1A2 (SULT1A2) increases the sulfation of Resveratrol.	[18]
Catechol	DML0YEK	Investigative	Sulfotransferase 1A2 (SULT1A2) increases the sulfation of Catechol.	[17]

13 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 Sulfotransferase 1A2 (SULT1A2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sulfotransferase 1A2 (SULT1A2).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sulfotransferase 1A2 (SULT1A2).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sulfotransferase 1A2 (SULT1A2).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Sulfotransferase 1A2 (SULT1A2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sulfotransferase 1A2 (SULT1A2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sulfotransferase 1A2 (SULT1A2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sulfotransferase 1A2 (SULT1A2).	[14]

References

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• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [9] 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.
• [10] 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.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
• [17] Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs. Toxicol Appl Pharmacol. 2007 May 15;221(1):13-20. doi: 10.1016/j.taap.2007.02.013. Epub 2007 Feb 28.
• [18] Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1. Xenobiotica. 2005 Dec;35(12):1101-19. doi: 10.1080/00498250500354253.
• [19] Intestinal carcinogenesis of two food processing contaminants, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 5-hydroxymethylfurfural, in transgenic FVB min mice expressing human sulfotransferases. Mol Carcinog. 2012 Dec;51(12):984-92. doi: 10.1002/mc.20869. Epub 2011 Oct 17.
• [20] Altered tissue distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adducts in mice transgenic for human sulfotransferases 1A1 and 1A2. Carcinogenesis. 2011 Nov;32(11):1734-40. doi: 10.1093/carcin/bgr204. Epub 2011 Sep 7.
• [21] Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols. Cancer Res. 2005 Apr 1;65(7):2644-52. doi: 10.1158/0008-5472.CAN-04-3544.