Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEP6RV)

• DTT Name: Glutathione reductase (GR)
• Synonyms: Glutathione reductase, mitochondrial; GRase; GRD1; GLUR
• Gene Name: GSR
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Sulfur donor oxidoreductase
• UniProt ID: GSHR_HUMAN
• TTD ID: T30803
• EC Number: EC 1.8.1.7
• Sequence:
  MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAG
  AVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHS
  EFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDP
  KPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAG
  YIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKK
  TLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVD
  EFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPP
  IGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQ
  GLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR
• Function: Maintains high levels of reduced glutathione in the cytosol.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Thyroid hormone synthesis (hsa04918)
• Reactome Pathway:
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  Metabolism of ingested H2SeO4 and H2SeO3 into H2Se (R-HSA-2408550)
• BioCyc Pathway: MetaCyc:HS02602-MON

Molecular Interaction Atlas (MIA) of This DTT

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	[2]

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	[3]
Golden phosphorous acetyletic compound 1	DMVAKUI	N. A.	N. A.	Patented	[3]
Golden phosphorous acetyletic compound 2	DMYJ15A	N. A.	N. A.	Patented	[3]
Terpyridineplatinum(II) complexe 3	DM54EFD	N. A.	N. A.	Patented	[3]
Terpyridineplatinum(II) complexe 4	DMOV86T	N. A.	N. A.	Patented	[3]

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	[4]
2,4,6 trinitrobenzene sulfonate 1,3-bis (2-chlorethyl)-1-nitrosourea	DMTA152	Discovery agent	N.A.	Investigative	[2]
3,6-Dihydroxy-Xanthene-9-Propionic Acid	DM7AORH	Discovery agent	N.A.	Investigative	[5]
3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol	DMMOE40	Discovery agent	N.A.	Investigative	[5]
3-Sulfinoalanine	DMILTRN	N. A.	N. A.	Investigative	[5]
4-nitrobenzo[c][1,2,5]thiadiazole	DMKZJ1V	Discovery agent	N.A.	Investigative	[6]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[5]
Glutathionylspermidine Disulfide	DMPX7FR	Discovery agent	N.A.	Investigative	[5]
Meta-Nitro-Tyrosine	DMITMN9	Discovery agent	N.A.	Investigative	[5]
N-6060	DMDMI7P	Asthma	CA23	Investigative	[7]
N-6547	DM814EQ	Inflammatory bowel disease	DD72	Investigative	[7]
N-9xxx	DMML1J4	Vascular disease	BE2Z	Investigative	[7]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[5]
Trans-(1S(R),2S(R))-2-Hydroxycyclooctyl nitrate	DMYVJHN	Discovery agent	N.A.	Investigative	[8]
Trans-(R(S))-2-Hydroxy-1-phenylethyl nitrate	DMXC98D	Discovery agent	N.A.	Investigative	[8]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Glutathione reductase (GSR) DME Info
• Gene Name: GSR

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[9]

References

• [1] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [2] The purification and properties of glutathione reductase from the cestode Moniezia expansa. Int J Biochem Cell Biol. 1995 Apr;27(4):393-401.
• [3] Thioredoxin reductase inhibitors: a patent review.Expert Opin Ther Pat. 2017 May;27(5):547-556.
• [4] 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.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential antimalarial agents. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2283-92.
• [7] 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).
• [8] In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3661-3.
• [9] Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. Carcinogenesis. 1999 Sep;20(9):1657-66.