Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLA2WJT)

• DOT Name: Glutathione S-transferase Mu 3 (GSTM3)
• Synonyms: EC 2.5.1.18; GST class-mu 3; GSTM3-3; hGSTM3-3
• Gene Name: GSTM3
• Related Disease:
  Acute lymphocytic leukaemia
  Alzheimer disease
  Benign prostatic hyperplasia
  Bladder cancer
  Breast neoplasm
  Carcinoma of esophagus
  Castration-resistant prostate carcinoma
  Cholangiocarcinoma
  Chronic hepatitis B virus infection
  Clear cell renal carcinoma
  Colorectal carcinoma
  Cystic fibrosis
  Esophageal cancer
  Glaucoma/ocular hypertension
  Head and neck cancer
  Head and neck carcinoma
  High blood pressure
  Leukoplakia
  Lymphoma, non-Hodgkin, familial
  Neoplasm
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Oral cancer
  Osteoporosis
  Prostate cancer
  Skin cancer
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bone osteosarcoma
  Laryngeal carcinoma
  Meningioma
  Metastatic malignant neoplasm
  Osteosarcoma
  Pancreatic cancer
  Prostate carcinoma
  Cervical cancer
  Cervical carcinoma
  Colorectal neoplasm
  Adenocarcinoma
  Gallbladder carcinoma
  Prostate neoplasm
• UniProt ID: GSTM3_HUMAN
• PDB ID: 3GTU
• EC Number: 2.5.1.18
• Pfam ID: PF00043 ; PF02798
• Sequence:
  MSCESSMVLGYWDIRGLAHAIRLLLEFTDTSYEEKRYTCGEAPDYDRSQWLDVKFKLDLD
  FPNLPYLLDGKNKITQSNAILRYIARKHNMCGETEEEKIRVDIIENQVMDFRTQLIRLCY
  SSDHEKLKPQYLEELPGQLKQFSMFLGKFSWFAGEKLTFVDFLTYDILDQNRIFDPKCLD
  EFPNLKAFMCRFEALEKIAAYLQSDQFCKMPINNKMAQWGNKPVC
• Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers.
• Tissue Specificity: Testis and brain.
• 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

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[3]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[6]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Genetic Variation	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Posttranslational Modification	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[12]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[6]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[13]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[14]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[14]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[15]
Leukoplakia	DIST3QD3	Strong	Genetic Variation	[16]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[6]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[17]
Oral cancer	DISLD42D	Strong	Genetic Variation	[18]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[19]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[7]
Skin cancer	DISTM18U	Strong	Genetic Variation	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[21]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[4]
Bone osteosarcoma	DIST1004	moderate	Genetic Variation	[22]
Laryngeal carcinoma	DISNHCIV	moderate	Genetic Variation	[14]
Meningioma	DISPT4TG	moderate	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[24]
Osteosarcoma	DISLQ7E2	moderate	Genetic Variation	[22]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[7]
Cervical cancer	DISFSHPF	Disputed	Genetic Variation	[26]
Cervical carcinoma	DIST4S00	Disputed	Genetic Variation	[26]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[11]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[27]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[28]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[29]

This DOT Affected the Biotransformations of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Glutathione S-transferase Mu 3 (GSTM3) decreases the nitrosation of DTI-015.	[57]
Dinoprostone	DMTYOPD	Approved	Glutathione S-transferase Mu 3 (GSTM3) affects the chemical synthesis of Dinoprostone.	[58]
Mefenamic acid	DMK7HFI	Approved	Glutathione S-transferase Mu 3 (GSTM3) increases the glutathionylation of Mefenamic acid.	[60]

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	Glutathione S-transferase Mu 3 (GSTM3) affects the metabolism of Glutathione.	[59]
DNCB	DMDTVYC	Phase 2	Glutathione S-transferase Mu 3 (GSTM3) decreases the metabolism of DNCB.	[61]
Hexylacrolein	DMBC8KM	Investigative	Glutathione S-transferase Mu 3 (GSTM3) decreases the metabolism of Hexylacrolein.	[61]
PGH2	DMZFVGC	Investigative	Glutathione S-transferase Mu 3 (GSTM3) affects the metabolism of PGH2.	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aminohippuric acid	DMUN54G	Investigative	Glutathione S-transferase Mu 3 (GSTM3) increases the response to substance of Aminohippuric acid.	[62]

28 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 Glutathione S-transferase Mu 3 (GSTM3).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[39]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[40]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[35]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[41]
Tetracycline	DMZA017	Approved	Tetracycline decreases the activity of Glutathione S-transferase Mu 3 (GSTM3).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[43]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[45]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[47]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[48]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[49]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[51]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[52]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[53]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[44]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[54]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[55]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Glutathione S-transferase Mu 3 (GSTM3).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Glutathione S-transferase Mu 3 (GSTM3).	[50]

References

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