Details of Drug Off-Target (DOT)

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

• DOT Name: Glutathione S-transferase theta-1 (GSTT1)
• Synonyms: EC 2.5.1.18; GST class-theta-1; Glutathione transferase T1-1
• Gene Name: GSTT1
• UniProt ID: GSTT1_HUMAN
• PDB ID: 2C3N; 2C3Q; 2C3T
• EC Number: 2.5.1.18
• Pfam ID: PF00043 ; PF13417
• Sequence:
  MGLELYLDLLSQPCRAVYIFAKKNDIPFELRIVDLIKGQHLSDAFAQVNPLKKVPALKDG
  DFTLTESVAILLYLTRKYKVPDYWYPQDLQARARVDEYLAWQHTTLRRSCLRALWHKVMF
  PVFLGEPVSPQTLAATLAELDVTLQLLEDKFLQNKAFLTGPHISLADLVAITELMHPVGA
  GCQVFEGRPKLATWRQRVEAAVGEDLFQEAHEVILKAKDFPPADPTIKQKLMPWVLAMIR
• Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide.
• Tissue Specificity: Found in erythrocyte. Expressed at low levels in liver. In lung, expressed at low levels in club cells and ciliated cells at the alveolar/bronchiolar junction. Absent from epithelial cells of larger bronchioles.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Platinum drug resistance (hsa01524)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Paracetamol ADME (R-HSA-9753281)
  Glutathione conjugation (R-HSA-156590)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Troglitazone	DM3VFPD	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Troglitazone.	[15]
Hydroquinone	DM6AVR4	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Hydroquinone.	[16]
Ethanol	DMDRQZU	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Ethanol.	[17]
Methamphetamine	DMPM4SK	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Methamphetamine.	[19]
Vitamin C	DMXJ7O8	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Vitamin C.	[20]
Paraquat	DMR8O3X	Investigative	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Paraquat.	[22]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE.	[23]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Glutathione S-transferase theta-1 (GSTT1) increases the response to substance of Rapamycin Immunosuppressant Drug.	[24]
Aminohippuric acid	DMUN54G	Investigative	Glutathione S-transferase theta-1 (GSTT1) decreases the activity of Aminohippuric acid.	[25]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Hydroxydimethylarsine Oxide.	[27]
Deoxythymidine	DMR90HY	Investigative	Glutathione S-transferase theta-1 (GSTT1) affects the response to substance of Deoxythymidine.	[28]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Glutathione S-transferase theta-1 (GSTT1) decreases the nitrosation of DTI-015.	[18]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	Glutathione S-transferase theta-1 (GSTT1) affects the metabolism of Glutathione.	[21]
Uric acid	DMA1MKT	Investigative	Glutathione S-transferase theta-1 (GSTT1) affects the abundance of Uric acid.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glutathione S-transferase theta-1 (GSTT1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glutathione S-transferase theta-1 (GSTT1).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Glutathione S-transferase theta-1 (GSTT1).	[9]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Glutathione S-transferase theta-1 (GSTT1).	[8]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Glutathione S-transferase theta-1 (GSTT1).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Glutathione S-transferase theta-1 (GSTT1).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Glutathione S-transferase theta-1 (GSTT1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glutathione S-transferase theta-1 (GSTT1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutathione S-transferase theta-1 (GSTT1).	[12]

References

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• [20] Functional genetic variants of glutathione S-transferase protect against serum ascorbic acid deficiency. Am J Clin Nutr. 2009 Nov;90(5):1411-7. doi: 10.3945/ajcn.2009.28327. Epub 2009 Aug 26.
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