Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPY3OKU)

• DOT Name: Thioredoxin reductase 1, cytoplasmic
• Synonyms: TR; EC 1.8.1.9; Gene associated with retinoic and interferon-induced mortality 12 protein; GRIM-12; Gene associated with retinoic and IFN-induced mortality 12 protein; KM-102-derived reductase-like factor; Peroxidase TXNRD1; EC 1.11.1.2; Thioredoxin reductase TR1
• Gene Name: TXNRD1
• UniProt ID: TRXR1_HUMAN
• PDB ID: 2CFY; 2J3N; 2ZZ0; 2ZZB; 2ZZC; 3QFA; 3QFB; 7X1R
• EC Number: 1.11.1.2; 1.8.1.9
• Pfam ID: PF00462 ; PF07992 ; PF02852
• Sequence:
  MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
  AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
  PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
  AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
  EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
  IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
  GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
  AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
  AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
  VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
  GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG
• Function: Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2) ; [Isoform 1]: Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions; [Isoform 4]: Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2; [Isoform 5]: Enhances the transcriptional activity of the estrogen receptor ESR2 only. Mediates cell death induced by a combination of interferon-beta and retinoic acid.
• Tissue Specificity: .Expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines.; [Isoform 4]: Widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver.
• 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)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Avastin+/-Tarceva	DMA86FL	Phase 3	Thioredoxin reductase 1, cytoplasmic increases the reduction of Avastin+/-Tarceva.	[66]
THIOCTIC ACID	DMNFCXW	Investigative	Thioredoxin reductase 1, cytoplasmic increases the reduction of THIOCTIC ACID.	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Thioredoxin reductase 1, cytoplasmic.	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Thioredoxin reductase 1, cytoplasmic.	[43]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Thioredoxin reductase 1, cytoplasmic.	[46]

84 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Thioredoxin reductase 1, cytoplasmic.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Thioredoxin reductase 1, cytoplasmic.	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thioredoxin reductase 1, cytoplasmic.	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[14]
Marinol	DM70IK5	Approved	Marinol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[15]
Selenium	DM25CGV	Approved	Selenium increases the activity of Thioredoxin reductase 1, cytoplasmic.	[16]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Thioredoxin reductase 1, cytoplasmic.	[17]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Thioredoxin reductase 1, cytoplasmic.	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Thioredoxin reductase 1, cytoplasmic.	[21]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Thioredoxin reductase 1, cytoplasmic.	[22]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[23]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Thioredoxin reductase 1, cytoplasmic.	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Thioredoxin reductase 1, cytoplasmic.	[25]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[25]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Thioredoxin reductase 1, cytoplasmic.	[25]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[25]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Thioredoxin reductase 1, cytoplasmic.	[26]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Thioredoxin reductase 1, cytoplasmic.	[26]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Thioredoxin reductase 1, cytoplasmic.	[27]
Bosentan	DMIOGBU	Approved	Bosentan increases the expression of Thioredoxin reductase 1, cytoplasmic.	[28]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Thioredoxin reductase 1, cytoplasmic.	[29]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[30]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid increases the expression of Thioredoxin reductase 1, cytoplasmic.	[31]
Flucloxacillin	DMNUWST	Approved	Flucloxacillin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[29]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Thioredoxin reductase 1, cytoplasmic.	[32]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the activity of Thioredoxin reductase 1, cytoplasmic.	[33]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[27]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[34]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Thioredoxin reductase 1, cytoplasmic.	[35]
HMPL-004	DM29XGY	Phase 3	HMPL-004 decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[36]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[36]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Thioredoxin reductase 1, cytoplasmic.	[37]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[38]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Thioredoxin reductase 1, cytoplasmic.	[39]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[6]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[16]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Thioredoxin reductase 1, cytoplasmic.	[40]
APR-246	DMNFADH	Phase 2	APR-246 decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[41]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
CERC-801	DM3SZ7P	Phase 2	CERC-801 decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Thioredoxin reductase 1, cytoplasmic.	[44]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Thioredoxin reductase 1, cytoplasmic.	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[37]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Thioredoxin reductase 1, cytoplasmic.	[47]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[48]
Taxifolin	DMQJSF9	Preclinical	Taxifolin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[49]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Thioredoxin reductase 1, cytoplasmic.	[51]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Thioredoxin reductase 1, cytoplasmic.	[52]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[53]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[54]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Thioredoxin reductase 1, cytoplasmic.	[38]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Thioredoxin reductase 1, cytoplasmic.	[55]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[56]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[57]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Thioredoxin reductase 1, cytoplasmic.	[58]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Thioredoxin reductase 1, cytoplasmic.	[59]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Thioredoxin reductase 1, cytoplasmic.	[60]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[61]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol decreases the expression of Thioredoxin reductase 1, cytoplasmic.	[36]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[53]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 increases the expression of Thioredoxin reductase 1, cytoplasmic.	[53]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
Plumbagin	DM9BS50	Investigative	Plumbagin increases the expression of Thioredoxin reductase 1, cytoplasmic.	[62]
2-Propanol, Isopropanol	DML5O0H	Investigative	2-Propanol, Isopropanol increases the expression of Thioredoxin reductase 1, cytoplasmic.	[24]
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine increases the expression of Thioredoxin reductase 1, cytoplasmic.	[63]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Thioredoxin reductase 1, cytoplasmic.	[64]
Edetic acid	DM10D85	Investigative	Edetic acid increases the activity of Thioredoxin reductase 1, cytoplasmic.	[65]

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