Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTR7UJ3)

• DTT Name: Cytoplasmic thioredoxin reductase (TXNRD1)
• Synonyms: Thioredoxin reductase TR1; Thioredoxin reductase 1, cytoplasmic; KM-102-derived reductase-like factor; KDRF; Gene associated with retinoic and interferon-induced mortality 12 protein; Gene associated with retinoic and IFN-induced mortality 12 protein; GRIM12; GRIM-12
• Gene Name: TXNRD1
• DTT Type: Successful target; [1]
• BioChemical Class: Sulfur donor oxidoreductase
• UniProt ID: TRXR1_HUMAN
• TTD ID: T84581
• EC Number: EC 1.8.1.9
• Sequence:
  MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
  AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
  PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
  AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
  EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
  IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
  GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
  AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
  AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
  VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
  GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG
• Function: Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
• KEGG Pathway:
  Selenocompound metabolism (hsa00450)
  Pathways in cancer (hsa05200)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  Metabolism of ingested H2SeO4 and H2SeO3 into H2Se (R-HSA-2408550)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  Interconversion of nucleotide di- and triphosphates (R-HSA-499943)
  Metabolism of ingested MeSeO2H into MeSeH (R-HSA-5263617)
  Uptake and function of diphtheria toxin (R-HSA-5336415)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fotemustine	DMV62ED	Solid tumour/cancer	2A00-2F9Z	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Spermidine	DMVJNFI	Plaque psoriasis	EA90.0	Phase 3	[1]

57 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-aryl quinol derivative 1	DMEMYDZ	N. A.	N. A.	Patented	[2]
4-aryl quinol derivative 2	DM7TW5Z	N. A.	N. A.	Patented	[2]
4-aryl quinol derivative 3	DM05V8Q	N. A.	N. A.	Patented	[2]
4-aryl quinol derivative 4	DM5IWX2	N. A.	N. A.	Patented	[2]
4-aryl quinol derivative 5	DMWB2YX	N. A.	N. A.	Patented	[2]
4-aryl quinol derivative 7	DMC3KTB	N. A.	N. A.	Patented	[2]
Acyl oxymethyl acrylamide ester derivative 1	DMXTUE1	N. A.	N. A.	Patented	[2]
Acyl oxymethyl acrylamide ester derivative 2	DMU8OIL	N. A.	N. A.	Patented	[2]
Benzisoselenazolone difluorocytidine derivative 1	DMF01AR	N. A.	N. A.	Patented	[2]
Binuclear gold(I) compound 1	DM5WN0U	N. A.	N. A.	Patented	[2]
Binuclear gold(I) compound 2	DM5WAGC	N. A.	N. A.	Patented	[2]
Binuclear gold(I) compound 3	DM94TKW	N. A.	N. A.	Patented	[2]
Bis-sulfonamide derivative 1	DMLV9UR	N. A.	N. A.	Patented	[2]
Bis-sulfonamide derivative 2	DMR0ANI	N. A.	N. A.	Patented	[2]
Disulfide compound 1	DMTYL68	N. A.	N. A.	Patented	[2]
Disulfide compound 2	DM6ON31	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]
Golden phosphorous acetyletic compound 3	DMRUCK8	N. A.	N. A.	Patented	[2]
Metal complex derivative 1	DMUOW3T	N. A.	N. A.	Patented	[2]
Metal complex derivative 2	DM0BTH8	N. A.	N. A.	Patented	[2]
Metal complex derivative 3	DM31BMP	N. A.	N. A.	Patented	[2]
Palmarumycin derivative 1	DM859ZQ	N. A.	N. A.	Patented	[2]
Palmarumycin derivative 2	DMRLWZI	N. A.	N. A.	Patented	[2]
Palmarumycin derivative 3	DM198BY	N. A.	N. A.	Patented	[2]
Palmarumycin derivative 4	DMZGI0R	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-17	DMTI5E3	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-18	DMIA3GH	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-19	DM5JSI3	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-27	DMVYO09	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-28	DM67NBI	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-29	DMIF7KG	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-30	DMWHAKG	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-31	DMBL5J9	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-32	DMZNM52	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-39	DM0LB21	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-42	DML4C6D	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-43	DMTFLVN	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-44	DM9S2UP	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-45	DMSZ0GE	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-46	DMGF04T	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-47	DMI61KF	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-48	DM4EFRL	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-5	DMTUNW4	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-6	DMCUAO9	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-7	DMWIMN9	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-8	DMYFV3D	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-Figure4b	DMJ6CI5	N. A.	N. A.	Patented	[2]
PMID27977313-Compound-Figure6C	DMICBFK	N. A.	N. A.	Patented	[2]
Terpyridineplatinum(II) complexe 1	DMFMZCW	N. A.	N. A.	Patented	[2]
Terpyridineplatinum(II) complexe 2	DMLUYR0	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]
Terpyridineplatinum(II) complexe 5	DMI4MJ2	N. A.	N. A.	Patented	[2]
Triazole gold complexe 1	DMCWES7	N. A.	N. A.	Patented	[2]
Triazole gold complexe 2	DMJON7D	N. A.	N. A.	Patented	[2]
Triazole gold complexe 3	DM5TILQ	N. A.	N. A.	Patented	[2]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-formyl-4-phenyl-1,2,5-oxadiazole 2-oxide	DM8RY7G	Discovery agent	N.A.	Investigative	[3]
4,6-dinitrobenzo[c][1,2,5]thiadiazole	DMWDYLR	Discovery agent	N.A.	Investigative	[4]
5,8-Dihydroxy-1,4-naphthoquinone	DMOCEPA	Malaria	1F40-1F45	Investigative	[5]
Bis(2,4-dinitrophenyl)sulfane	DMEW49T	Discovery agent	N.A.	Investigative	[4]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[1]

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

• DTT DME Name: Thioredoxin reductase TR1 (TXNRD1) DME Info
• Gene Name: TXNRD1

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	[6]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenious acid	DMB7GPA	N. A.	N. A.	Investigative	[6]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Thioredoxin reductase inhibitors: a patent review.Expert Opin Ther Pat. 2017 May;27(5):547-556.
• [3] Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schis... J Med Chem. 2009 Oct 22;52(20):6474-83.
• [4] Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential antimalarial agents. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2283-92.
• [5] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [6] Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. Carcinogenesis. 1999 Sep;20(9):1657-66.