Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ1USIA)

• DOT Name: Glutathione S-transferase A4 (GSTA4)
• Synonyms: EC 2.5.1.18; GST class-alpha member 4; Glutathione S-transferase A4-4
• Gene Name: GSTA4
• UniProt ID: GSTA4_HUMAN
• PDB ID: 1GUL; 1GUM; 3IK7
• EC Number: 2.5.1.18
• Pfam ID: PF14497 ; PF02798
• Sequence:
  MAARPKLHYPNGRGRMESVRWVLAAAGVEFDEEFLETKEQLYKLQDGNHLLFQQVPMVEI
  DGMKLVQTRSILHYIADKHNLFGKNLKERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKE
  VVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTILALEEKIPNILSAFPF
  LQEYTVKLSNIPTIKRFLEPGSKKKPPPDEIYVRTVYNIFRP
• Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).
• Tissue Specificity: Expressed at a high level in brain, placenta, and skeletal muscle and much lower in lung and 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: 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
Fluorouracil	DMUM7HZ	Approved	Glutathione S-transferase A4 (GSTA4) affects the response to substance of Fluorouracil.	[26]

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 A4 (GSTA4) affects the metabolism of Glutathione.	[27]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Glutathione S-transferase A4 (GSTA4) affects the metabolism of 4-hydroxy-2-nonenal.	[16]

26 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 A4 (GSTA4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase A4 (GSTA4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glutathione S-transferase A4 (GSTA4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione S-transferase A4 (GSTA4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione S-transferase A4 (GSTA4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Glutathione S-transferase A4 (GSTA4).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glutathione S-transferase A4 (GSTA4).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glutathione S-transferase A4 (GSTA4).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Glutathione S-transferase A4 (GSTA4).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Glutathione S-transferase A4 (GSTA4).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glutathione S-transferase A4 (GSTA4).	[10]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Glutathione S-transferase A4 (GSTA4).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the activity of Glutathione S-transferase A4 (GSTA4).	[12]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Glutathione S-transferase A4 (GSTA4).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione S-transferase A4 (GSTA4).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Glutathione S-transferase A4 (GSTA4).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin increases the activity of Glutathione S-transferase A4 (GSTA4).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Glutathione S-transferase A4 (GSTA4).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutathione S-transferase A4 (GSTA4).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Glutathione S-transferase A4 (GSTA4).	[20]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Glutathione S-transferase A4 (GSTA4).	[21]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Glutathione S-transferase A4 (GSTA4).	[22]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Glutathione S-transferase A4 (GSTA4).	[23]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of Glutathione S-transferase A4 (GSTA4).	[24]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Glutathione S-transferase A4 (GSTA4).	[15]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide increases the expression of Glutathione S-transferase A4 (GSTA4).	[25]

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 increases the methylation of Glutathione S-transferase A4 (GSTA4).	[17]

References

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