Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGN1KVZ)

• DOT Name: Microsomal glutathione S-transferase 1 (MGST1)
• Synonyms: Microsomal GST-1; EC 2.5.1.18; Microsomal GST-I
• Gene Name: MGST1
• UniProt ID: MGST1_HUMAN
• EC Number: 2.5.1.18
• Pfam ID: PF01124
• Sequence:
  MVDLTQVMDDEVFMAFASYATIILSKMMLMSTATAFYRLTRKVFANPEDCVAFGKGENAK
  KYLRTDDRVERVRRAHLNDLENIIPFLGIGLLYSLSGPDPSTAILHFRLFVGARIYHTIA
  YLTPLPQPNRALSFFVGYGVTLSMAYRLLKSKLYL
• Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
• Tissue Specificity: Highly expressed in liver.
• 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:
  Aflatoxin activation and detoxification (R-HSA-5423646)
  Neutrophil degranulation (R-HSA-6798695)
  Glutathione conjugation (R-HSA-156590)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Microsomal glutathione S-transferase 1 (MGST1) decreases the response to substance of Cisplatin.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Microsomal glutathione S-transferase 1 (MGST1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microsomal glutathione S-transferase 1 (MGST1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Microsomal glutathione S-transferase 1 (MGST1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Microsomal glutathione S-transferase 1 (MGST1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[13]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[14]
Methimazole	DM25FL8	Approved	Methimazole increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[16]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[17]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[18]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[4]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A affects the expression of Microsomal glutathione S-transferase 1 (MGST1).	[23]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Microsomal glutathione S-transferase 1 (MGST1).	[24]

References

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• [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.
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• [13] Survival of retinal pigment epithelium after exposure to prolonged oxidative injury: a detailed gene expression and cellular analysis. Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3767-77.
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• [21] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [22] 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.
• [23] Microphysiological system modeling of ochratoxin A-associated nephrotoxicity. Toxicology. 2020 Nov;444:152582. doi: 10.1016/j.tox.2020.152582. Epub 2020 Sep 6.
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• [25] Multiple roles of microsomal glutathione transferase 1 in cellular protection: a mechanistic study. Free Radic Biol Med. 2010 Dec 1;49(11):1638-45. doi: 10.1016/j.freeradbiomed.2010.08.013. Epub 2010 Aug 19.