Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0K7JIE)

• DOT Name: Sulfotransferase 1A1 (SULT1A1)
• Synonyms: ST1A1; EC 2.8.2.1; Aryl sulfotransferase 1; HAST1/HAST2; Phenol sulfotransferase 1; Phenol-sulfating phenol sulfotransferase 1; P-PST 1; ST1A3; Thermostable phenol sulfotransferase; Ts-PST
• Gene Name: SULT1A1
• UniProt ID: ST1A1_HUMAN
• PDB ID: 1LS6; 1Z28; 2D06; 3QVU; 3QVV; 3U3J; 3U3K; 3U3M; 3U3O; 3U3R; 4GRA
• EC Number: 2.8.2.1
• Pfam ID: PF00685
• Sequence:
  MELIQDTSRPPLEYVKGVPLIKYFAEALGPLQSFQARPDDLLISTYPKSGTTWVSQILDM
  IYQGGDLEKCHRAPIFMRVPFLEFKAPGIPSGMETLKDTPAPRLLKTHLPLALLPQTLLD
  QKVKVVYVARNAKDVAVSYYHFYHMAKVHPEPGTWDSFLEKFMVGEVSYGSWYQHVQEWW
  ELSRTHPVLYLFYEDMKENPKREIQKILEFVGRSLPEETVDFVVQHTSFKEMKKNPMTNY
  TTVPQEFMDHSISPFMRKGMAGDWKTTFTVAQNERFDADYAEKMAGCSLSFRSEL
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine groupe. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Displays broad substrate specificity for small phenolic compounds. Plays an important role in the sulfonation of endogenous molecules such as steroid hormones and 3,3'-diiodothyronin. Mediates the sulfate conjugation of a variety of xenobiotics, including the drugs acetaminophen and minoxidil. Mediates also the metabolic activation of carcinogenic N-hydroxyarylamines leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis. May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system.
• Tissue Specificity: Liver, lung, adrenal, brain, platelets and skin.
• KEGG Pathway: Chemical carcinogenesis - D. adducts (hsa05204)
• Reactome Pathway:
  Paracetamol ADME (R-HSA-9753281)
  Cytosolic sulfonation of small molecules (R-HSA-156584)
• BioCyc Pathway: MetaCyc:HS09898-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Sulfotransferase 1A1 (SULT1A1) affects the response to substance of Cisplatin.	[27]
Vinblastine	DM5TVS3	Approved	Sulfotransferase 1A1 (SULT1A1) affects the response to substance of Vinblastine.	[27]
5-hydroxymethyl-2-furfural	DMPFVJB	Phase 2	Sulfotransferase 1A1 (SULT1A1) increases the activity of 5-hydroxymethyl-2-furfural.	[37]
Nitrobenzanthrone	DMN6L70	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the activity of Nitrobenzanthrone.	[39]
Hydroxymethylpyrene	DMPGAR2	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the activity of Hydroxymethylpyrene.	[41]

This DOT Affected the Biotransformations of 24 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Estradiol.	[28]
Triclosan	DMZUR4N	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Triclosan.	[29]
Troglitazone	DM3VFPD	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Troglitazone.	[28]
Liothyronine	DM6IR3P	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Liothyronine.	[31]
Ropivacaine	DMSPJG2	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Ropivacaine.	[32]
Lidocaine	DML4ZOT	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Lidocaine.	[32]
Phentolamine	DMXYJOB	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Phentolamine.	[28]
Benzyl alcohol	DMBVYDI	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Benzyl alcohol.	[34]
Minoxidil	DMA2Z4F	Approved	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Minoxidil.	[28]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of 3,4-Dihydroxycinnamic Acid.	[35]
PINOCEMBRIN	DM96VWD	Phase 2	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of PINOCEMBRIN.	[28]
LM-94	DMW3QGJ	Phase 1/2	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of LM-94.	[28]
Steroid derivative 1	DMB0NVQ	Patented	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Steroid derivative 1.	[38]
Rutin	DMEHRAJ	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Rutin.	[38]
Chrysin	DM7V2LG	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Chrysin.	[40]
CATECHIN	DMY38SB	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of CATECHIN.	[40]
Apigenin	DMI3491	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Apigenin.	[40]
Serotonin	DMOFCRY	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Serotonin.	[28]
Catechol	DML0YEK	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Catechol.	[35]
L-thyroxine	DM83HWL	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of L-thyroxine.	[31]
2-hydroxy-17beta-estradiol	DMM9Z0B	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of 2-hydroxy-17beta-estradiol.	[38]
7-hydroxycoumarin	DMTMNO7	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of 7-hydroxycoumarin.	[28]
5-hydroxyindole	DMI0GMB	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of 5-hydroxyindole.	[28]
Hydroxytryptophol	DMZN3GP	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the sulfation of Hydroxytryptophol.	[28]

This DOT Affected the Regulation of Drug Effects of 10 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Diethylstilbestrol	DMN3UXQ	Approved	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Diethylstilbestrol.	[30]
Ethinyl estradiol	DMODJ40	Approved	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Ethinyl estradiol.	[30]
Estrone	DM5T6US	Approved	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Estrone.	[30]
Dopamine	DMPGUCF	Approved	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Dopamine.	[30]
Ammonia	DMOEVK6	Approved	Sulfotransferase 1A1 (SULT1A1) affects the metabolism of Ammonia.	[33]
Afimoxifene	DMFORDT	Phase 2	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Afimoxifene.	[36]
(Z)-endoxifen	DMGDOS2	Phase 2	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of (Z)-endoxifen.	[36]
Aminohippuric acid	DMUN54G	Investigative	Sulfotransferase 1A1 (SULT1A1) affects the metabolism of Aminohippuric acid.	[33]
N-nonylphenol	DMH3OUX	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of N-nonylphenol.	[30]
Mononitrophenol	DM4QO9G	Investigative	Sulfotransferase 1A1 (SULT1A1) increases the metabolism of Mononitrophenol.	[30]

31 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 1A1 (SULT1A1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sulfotransferase 1A1 (SULT1A1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sulfotransferase 1A1 (SULT1A1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Sulfotransferase 1A1 (SULT1A1).	[9]
Ethanol	DMDRQZU	Approved	Ethanol decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[10]
Piroxicam	DMTK234	Approved	Piroxicam decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[11]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[12]
Mefenamic acid	DMK7HFI	Approved	Mefenamic acid decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[13]
Meclofenamic acid	DM05FXR	Approved	Meclofenamic acid decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sulfotransferase 1A1 (SULT1A1).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sulfotransferase 1A1 (SULT1A1).	[15]
Lithium	DMZ3OU6	Phase 2	Lithium decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sulfotransferase 1A1 (SULT1A1).	[18]
4-Hydroxybenzoicacid	DM3WQNY	Patented	4-Hydroxybenzoicacid increases the activity of Sulfotransferase 1A1 (SULT1A1).	[19]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[20]
Nimesulide	DMR1NMD	Terminated	Nimesulide decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sulfotransferase 1A1 (SULT1A1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sulfotransferase 1A1 (SULT1A1).	[23]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[24]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the activity of Sulfotransferase 1A1 (SULT1A1).	[19]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Sulfotransferase 1A1 (SULT1A1).	[25]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Sulfotransferase 1A1 (SULT1A1).	[26]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid increases the activity of Sulfotransferase 1A1 (SULT1A1).	[19]
Aloe-emodin	DMPTY8S	Investigative	Aloe-emodin decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[20]
RHEIN	DMS6IJ0	Investigative	RHEIN decreases the activity of Sulfotransferase 1A1 (SULT1A1).	[20]

1 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 1A1 (SULT1A1).	[17]

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