Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6XU6VW)

• DOT Name: Thioredoxin
• Synonyms: Trx; ATL-derived factor; ADF; Surface-associated sulphydryl protein; SASP; allergen Hom s Trx
• Gene Name: TXN
• UniProt ID: THIO_HUMAN
• PDB ID: 1AIU ; 1AUC ; 1CQG ; 1CQH ; 1ERT ; 1ERU ; 1ERV ; 1ERW ; 1M7T ; 1MDI ; 1MDJ ; 1MDK ; 1TRS ; 1TRU ; 1TRV ; 1TRW ; 2HSH ; 2HXK ; 2IFQ ; 2IIY ; 3E3E ; 3KD0 ; 3M9J ; 3M9K ; 3QFA ; 3QFB ; 3TRX ; 4LL1 ; 4LL4 ; 4OO4 ; 4OO5 ; 4POK ; 4POL ; 4POM ; 4PUF ; 4TRX ; 5DQY
• Pfam ID: PF00085
• Sequence:
  MVKQIESKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVD
  DCQDVASECEVKCMPTFQFFKKGQKVGEFSGANKEKLEATINELV
• Function: Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity ; ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Parkinson disease (hsa05012)
  Salmonella infection (hsa05132)
  Fluid shear stress and atherosclerosis (hsa05418)
• 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)
  Protein repair (R-HSA-5676934)
  The NLRP3 inflammasome (R-HSA-844456)
  Regulation of FOXO transcriptional activity by acetylation (R-HSA-9617629)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Thioredoxin affects the response to substance of Arsenic.	[44]
Methamphetamine	DMPM4SK	Approved	Thioredoxin decreases the response to substance of Methamphetamine.	[45]
Paraquat	DMR8O3X	Investigative	Thioredoxin decreases the response to substance of Paraquat.	[46]

53 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.	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Thioredoxin.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thioredoxin.	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Thioredoxin.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thioredoxin.	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thioredoxin.	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thioredoxin.	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Thioredoxin.	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Thioredoxin.	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Thioredoxin.	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Thioredoxin.	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Thioredoxin.	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Thioredoxin.	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Thioredoxin.	[15]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Thioredoxin.	[16]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Thioredoxin.	[17]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Thioredoxin.	[16]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Thioredoxin.	[16]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Thioredoxin.	[18]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of Thioredoxin.	[19]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the expression of Thioredoxin.	[20]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Thioredoxin.	[15]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid increases the expression of Thioredoxin.	[21]
Atenolol	DMNKG1Z	Approved	Atenolol increases the expression of Thioredoxin.	[22]
Salicyclic acid	DM2F8XZ	Approved	Salicyclic acid increases the expression of Thioredoxin.	[15]
Mechlorethamine	DM0CVXA	Approved	Mechlorethamine decreases the activity of Thioredoxin.	[23]
Selegiline	DM6034S	Approved	Selegiline increases the expression of Thioredoxin.	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Thioredoxin.	[25]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Thioredoxin.	[25]
I3C	DMIGFOR	Phase 3	I3C decreases the expression of Thioredoxin.	[26]
Guaiacol	DMN4E7T	Phase 3	Guaiacol increases the expression of Thioredoxin.	[25]
Triptolide	DMCMDVR	Phase 3	Triptolide decreases the expression of Thioredoxin.	[27]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Thioredoxin.	[25]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Thioredoxin.	[28]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Thioredoxin.	[29]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the expression of Thioredoxin.	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thioredoxin.	[30]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the expression of Thioredoxin.	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Thioredoxin.	[33]
Benzylcinnamate	DMD7Z3H	Patented	Benzylcinnamate increases the expression of Thioredoxin.	[15]
MANUMYCIN A	DM1SWOY	Terminated	MANUMYCIN A decreases the expression of Thioredoxin.	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Thioredoxin.	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Thioredoxin.	[15]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the activity of Thioredoxin.	[38]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Thioredoxin.	[39]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Thioredoxin.	[40]
acrolein	DMAMCSR	Investigative	acrolein decreases the activity of Thioredoxin.	[41]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Thioredoxin.	[15]
	DM9CEI5		increases the expression of Thioredoxin.	[19]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid increases the expression of Thioredoxin.	[25]
hydroxycitronellal	DMFHCV9	Investigative	hydroxycitronellal increases the expression of Thioredoxin.	[15]
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine	DMPWB8G	Investigative	1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine decreases the expression of Thioredoxin.	[42]
Perillaldehyde	DMZA0VD	Investigative	Perillaldehyde increases the expression of Thioredoxin.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the oxidation of Thioredoxin.	[9]
DNCB	DMDTVYC	Phase 2	DNCB increases the oxidation of Thioredoxin.	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Thioredoxin.	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the methylation of Thioredoxin.	[36]
Diamide	DMOCQ9J	Investigative	Diamide increases the oxidation of Thioredoxin.	[9]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol affects the localization of Thioredoxin.	[10]
D-glucose	DMMG2TO	Investigative	D-glucose increases the secretion of Thioredoxin.	[37]

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