Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEGDPL2)

• DME Name: Glutathione reductase (GSR)
• Synonyms: Mitochondrial glutathione reductase; GLUR; GR; GRD1; GRase; GSR
• Gene Name: GSR
• UniProt ID: GSHR_HUMAN
• INTEDE ID: DME0110
• Gene ID: 2936
• EC Number:
  EC: 1.8.1.7
  Oxidoreductase
  Sulfur donor oxidoreductase
  NAD/NADP acceptor oxidoreductase
  EC: 1.8.1.7
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAG
  AVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHS
  EFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDP
  KPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAG
  YIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKK
  TLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVD
  EFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPP
  IGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQ
  GLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR
• Function: This enzyme catalyzes the reduction of glutathione disulfide (GSSG) to the sulfhydryl form glutathione (GSH), which is a critical molecule in resisting oxidative stress and maintaining the reducing environment of the cell.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Thyroid hormone synthesis (hsa04918)
• Reactome Pathway:
  Interconversion of nucleotide di- and triphosphates [P00390-2] (R-HSA-499943)
  Metabolism of ingested H2SeO4 and H2SeO3 into H2Se [P00390-2] (R-HSA-2408550)
  TP53 Regulates Metabolic Genes [P00390-2] (R-HSA-5628897)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)

Molecular Interaction Atlas (MIA) of This DME

1 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[8]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	7.83E-22	-5.55E-01	-1.47E+00
Alopecia	ED70	Skin from scalp	6.72E-01	4.16E-02	1.90E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.66E-06	-1.68E-01	-5.39E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.10E-01	2.14E-01	3.70E-01
Aortic stenosis	BB70	Calcified aortic valve	6.66E-01	-3.36E-02	-9.19E-02
Apnea	7A40	Hyperplastic tonsil	7.33E-01	5.96E-01	1.57E+00
Arthropathy	FA00-FA5Z	Peripheral blood	7.99E-01	1.14E-02	5.15E-02
Asthma	CA23	Nasal and bronchial airway	2.78E-01	5.38E-03	1.01E-02
Atopic dermatitis	EA80	Skin	3.38E-01	4.33E-02	1.95E-01
Autism	6A02	Whole blood	1.40E-01	-8.71E-02	-2.44E-01
Autoimmune uveitis	9A96	Peripheral monocyte	8.94E-02	-4.37E-01	-1.72E+00
Autosomal dominant monocytopenia	4B04	Whole blood	9.71E-01	1.72E-01	2.56E-01
Bacterial infection of gingival	1C1H	Gingival tissue	6.41E-05	2.00E-01	6.67E-01
Batten disease	5C56.1	Whole blood	9.87E-01	-3.03E-02	-1.54E-01
Behcet's disease	4A62	Peripheral blood	3.65E-01	3.55E-02	1.78E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	7.13E-02	-1.07E-01	-6.15E-01
Bladder cancer	2C94	Bladder tissue	4.73E-02	-1.84E-01	-7.76E-01
Breast cancer	2C60-2C6Z	Breast tissue	2.81E-92	6.68E-01	1.64E+00
Cardioembolic stroke	8B11.20	Whole blood	1.17E-02	1.16E-01	5.01E-01
Cervical cancer	2C77	Cervical tissue	4.72E-01	-2.13E-01	-4.67E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	9.87E-01	1.53E-02	4.16E-02
Chronic hepatitis C	1E51.1	Whole blood	3.37E-01	-7.32E-02	-3.01E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	4.94E-01	-1.38E-01	-3.35E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	5.29E-02	1.82E-01	3.37E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	3.34E-01	-1.61E-02	-7.68E-02
Colon cancer	2B90	Colon tissue	2.29E-49	-6.06E-01	-1.65E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.74E-01	9.39E-02	1.32E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	4.86E-01	-9.30E-02	-2.29E-01
Endometriosis	GA10	Endometrium tissue	5.57E-03	-3.28E-01	-8.25E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	8.78E-01	4.74E-02	1.61E-01
Familial hypercholesterolemia	5C80.00	Whole blood	3.51E-06	5.46E-01	1.47E+00
Gastric cancer	2B72	Gastric tissue	1.36E-01	1.17E+00	2.03E+00
Glioblastopma	2A00.00	Nervous tissue	2.47E-02	2.97E-02	8.07E-02
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	5.38E-01	-2.19E-01	-6.83E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	6.19E-03	9.70E-01	1.44E+00
Head and neck cancer	2D42	Head and neck tissue	3.95E-15	-8.32E-01	-1.41E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	9.19E-01	2.67E-02	1.04E-01
Huntington's disease	8A01.10	Whole blood	2.14E-01	-2.83E-01	-1.06E+00
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	2.98E-01	-3.14E-01	-9.09E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.37E-01	4.26E-02	4.04E-01
Influenza	1E30	Whole blood	5.02E-02	-9.96E-01	-1.56E+00
Interstitial cystitis	GC00.3	Bladder tissue	2.52E-02	-2.26E-01	-1.72E+00
Intracranial aneurysm	8B01.0	Intracranial artery	2.42E-04	4.89E-01	1.97E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.27E-01	-1.52E-01	-4.11E-01
Ischemic stroke	8B11	Peripheral blood	3.04E-01	-1.07E-01	-8.49E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	9.39E-01	-5.22E-02	-2.17E-01
Lateral sclerosis	8B60.4	Skin	4.40E-02	2.72E-01	2.18E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	1.74E-02	3.99E-01	1.71E+00
Liver cancer	2C12.0	Liver tissue	1.17E-07	3.41E-01	1.28E+00
Liver failure	DB99.7-DB99.8	Liver tissue	4.24E-01	2.48E-01	1.75E+00
Lung cancer	2C25	Lung tissue	1.48E-53	4.76E-01	1.32E+00
Lupus erythematosus	4A40	Whole blood	3.25E-08	5.10E-01	9.43E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.81E-01	-4.12E-02	-2.44E-01
Major depressive disorder	6A70-6A7Z	Whole blood	8.13E-02	6.11E-02	3.10E-01
Melanoma	2C30	Skin	3.72E-01	2.01E-01	2.61E-01
Multiple myeloma	2A83.1	Peripheral blood	8.40E-02	-2.43E-01	-1.01E+00
Multiple myeloma	2A83.1	Bone marrow	3.94E-04	6.38E-01	2.36E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	7.23E-01	-1.53E-02	-8.80E-02
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	5.81E-04	1.03E-01	4.29E-01
Myelofibrosis	2A20.2	Whole blood	4.56E-04	2.91E-01	1.85E+00
Myocardial infarction	BA41-BA50	Peripheral blood	6.07E-04	-1.16E-01	-2.93E-01
Myopathy	8C70.6	Muscle tissue	8.76E-04	4.72E-01	1.53E+00
Neonatal sepsis	KA60	Whole blood	5.58E-38	1.03E+00	3.17E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	3.32E-05	9.65E-01	2.09E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	9.07E-01	1.75E-01	3.53E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	3.56E-01	-7.48E-02	-2.78E-01
Olive pollen allergy	CA08.00	Peripheral blood	7.93E-01	2.35E-01	3.08E-01
Oral cancer	2B6E	Oral tissue	1.31E-01	-3.75E-01	-1.04E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	8.06E-02	5.95E-01	1.04E+00
Osteoporosis	FB83.1	Bone marrow	7.17E-01	-1.21E-01	-3.13E-01
Ovarian cancer	2C73	Ovarian tissue	5.18E-01	-3.02E-01	-6.63E-01
Pancreatic cancer	2C10	Pancreas	1.78E-03	2.77E-01	6.54E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	6.83E-01	1.03E-03	2.40E-03
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.48E-03	2.62E-01	1.03E+00
Pituitary cancer	2D12	Pituitary tissue	6.40E-01	8.37E-02	2.62E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	3.68E-01	2.75E-01	8.96E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.35E-02	8.54E-02	4.74E-01
Polycythemia vera	2A20.4	Whole blood	8.38E-01	1.90E-02	1.19E-01
Pompe disease	5C51.3	Biceps muscle	8.82E-06	1.43E+00	4.05E+00
Preterm birth	KA21.4Z	Myometrium	9.66E-02	-1.52E-01	-9.03E-01
Prostate cancer	2C82	Prostate	1.60E-01	2.27E-01	4.45E-01
Psoriasis	EA90	Skin	1.72E-12	-3.58E-01	-1.01E+00
Rectal cancer	2B92	Rectal colon tissue	1.49E-05	-6.26E-01	-3.33E+00
Renal cancer	2C90-2C91	Kidney	8.55E-01	-8.37E-02	-2.13E-01
Retinoblastoma	2D02.2	Uvea	1.64E-05	1.34E+00	8.71E+00
Rheumatoid arthritis	FA20	Synovial tissue	1.55E-03	4.77E-01	1.84E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	4.29E-01	1.58E-02	6.56E-02
Schizophrenia	6A20	Prefrontal cortex	5.67E-01	-4.37E-02	-6.67E-02
Schizophrenia	6A20	Superior temporal cortex	9.17E-01	-1.31E-02	-6.81E-02
Scleroderma	4A42.Z	Whole blood	2.68E-06	4.98E-01	3.43E+00
Seizure	8A60-8A6Z	Whole blood	3.28E-01	-1.05E-01	-7.41E-01
Sensitive skin	EK0Z	Skin	5.43E-01	1.18E-01	6.30E-01
Sepsis with septic shock	1G41	Whole blood	8.24E-94	1.06E+00	3.01E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	1.27E-01	-2.08E-01	-2.00E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	7.69E-02	4.10E-01	1.18E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	8.05E-01	-1.82E-02	-4.31E-02
Sjogren's syndrome	4A43.2	Salivary gland tissue	7.78E-01	-1.61E-01	-3.72E-01
Skin cancer	2C30-2C3Z	Skin	3.59E-25	5.32E-01	1.08E+00
Thrombocythemia	3B63	Whole blood	1.33E-01	-6.82E-02	-4.20E-01
Thrombocytopenia	3B64	Whole blood	1.72E-01	-2.09E-01	-6.07E-01
Thyroid cancer	2D10	Thyroid	1.98E-06	1.30E-01	4.05E-01
Tibial muscular dystrophy	8C75	Muscle tissue	2.30E-02	1.89E-01	4.97E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.33E-02	-5.55E-01	-1.73E+00
Type 2 diabetes	5A11	Liver tissue	3.08E-02	3.28E-01	1.52E+00
Ureter cancer	2C92	Urothelium	4.85E-01	9.31E-02	4.25E-01
Uterine cancer	2C78	Endometrium tissue	7.74E-01	-5.69E-02	-1.11E-01
Vitiligo	ED63.0	Skin	5.64E-01	-1.03E-01	-3.50E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Glutathione reductase (GR) DTT Info
• DME DTT Type: Patented-recorded

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxidized glutathione	DM9EQC0	Breast cancer	2C60-2C65	Approved	[1]

5 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acyl oxymethyl acrylamide ester derivative 1	DMXTUE1	N. A.	N. A.	Patented	[2]
Golden phosphorous acetyletic compound 1	DMVAKUI	N. A.	N. A.	Patented	[2]
Golden phosphorous acetyletic compound 2	DMYJ15A	N. A.	N. A.	Patented	[2]
Terpyridineplatinum(II) complexe 3	DM54EFD	N. A.	N. A.	Patented	[2]
Terpyridineplatinum(II) complexe 4	DMOV86T	N. A.	N. A.	Patented	[2]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(2'-chlorophenyl)penta-1,4-dien-3-one	DMKTZSY	Discovery agent	N.A.	Investigative	[3]
2,4,6 trinitrobenzene sulfonate 1,3-bis (2-chlorethyl)-1-nitrosourea	DMTA152	Discovery agent	N.A.	Investigative	[1]
3,6-Dihydroxy-Xanthene-9-Propionic Acid	DM7AORH	Discovery agent	N.A.	Investigative	[4]
3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol	DMMOE40	Discovery agent	N.A.	Investigative	[4]
3-Sulfinoalanine	DMILTRN	N. A.	N. A.	Investigative	[4]
4-nitrobenzo[c][1,2,5]thiadiazole	DMKZJ1V	Discovery agent	N.A.	Investigative	[5]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[4]
Glutathionylspermidine Disulfide	DMPX7FR	Discovery agent	N.A.	Investigative	[4]
Meta-Nitro-Tyrosine	DMITMN9	Discovery agent	N.A.	Investigative	[4]
N-6060	DMDMI7P	Asthma	CA23	Investigative	[6]
N-6547	DM814EQ	Inflammatory bowel disease	DD72	Investigative	[6]
N-9xxx	DMML1J4	Vascular disease	BE2Z	Investigative	[6]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[4]
Trans-(1S(R),2S(R))-2-Hydroxycyclooctyl nitrate	DMYVJHN	Discovery agent	N.A.	Investigative	[7]
Trans-(R(S))-2-Hydroxy-1-phenylethyl nitrate	DMXC98D	Discovery agent	N.A.	Investigative	[7]

References

• [1] The purification and properties of glutathione reductase from the cestode Moniezia expansa. Int J Biochem Cell Biol. 1995 Apr;27(4):393-401.
• [2] Thioredoxin reductase inhibitors: a patent review.Expert Opin Ther Pat. 2017 May;27(5):547-556.
• [3] Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem. 2005 Nov 17;48(23):7400-10.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential antimalarial agents. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2283-92.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2613).
• [7] In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3661-3.
• [8] Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. Carcinogenesis. 1999 Sep;20(9):1657-66.