Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46QN4B)

• DOT Name: Thioredoxin-interacting protein
• Synonyms: Thioredoxin-binding protein 2; Vitamin D3 up-regulated protein 1
• Gene Name: TXNIP
• UniProt ID: TXNIP_HUMAN
• PDB ID: 4GEI; 4GEJ; 4GFX; 4LL1; 4LL4; 4ROF; 4ROJ; 5CQ2; 5DF6; 5DWS; 5DZD
• Pfam ID: PF02752 ; PF00339
• Sequence:
  MVMFKKIKSFEVVFNDPEKVYGSGEKVAGRVIVEVCEVTRVKAVRILACGVAKVLWMQGS
  QQCKQTSEYLRYEDTLLLEDQPTGENEMVIMRPGNKYEYKFGFELPQGPLGTSFKGKYGC
  VDYWVKAFLDRPSQPTQETKKNFEVVDLVDVNTPDLMAPVSAKKEKKVSCMFIPDGRVSV
  SARIDRKGFCEGDEISIHADFENTCSRIVVPKAAIVARHTYLANGQTKVLTQKLSSVRGN
  HIISGTCASWRGKSLRVQKIRPSILGCNILRVEYSLLIYVSVPGSKKVILDLPLVIGSRS
  GLSSRTSSMASRTSSEMSWVDLNIPDTPEAPPCYMDVIPEDHRLESPTTPLLDDMDGSQD
  SPIFMYAPEFKFMPPPTYTEVDPCILNNNVQ
• Function: May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway:
  Regulation of FOXO transcriptional activity by acetylation (R-HSA-9617629)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  The NLRP3 inflammasome (R-HSA-844456)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Thioredoxin-interacting protein affects the response to substance of Topotecan.	[68]
Paraquat	DMR8O3X	Investigative	Thioredoxin-interacting protein increases the response to substance of Paraquat.	[69]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Thioredoxin-interacting protein.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thioredoxin-interacting protein.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thioredoxin-interacting protein.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thioredoxin-interacting protein.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thioredoxin-interacting protein.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thioredoxin-interacting protein.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thioredoxin-interacting protein.	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thioredoxin-interacting protein.	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Thioredoxin-interacting protein.	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Thioredoxin-interacting protein.	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Thioredoxin-interacting protein.	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Thioredoxin-interacting protein.	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Thioredoxin-interacting protein.	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Thioredoxin-interacting protein.	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thioredoxin-interacting protein.	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Thioredoxin-interacting protein.	[17]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Thioredoxin-interacting protein.	[18]
Marinol	DM70IK5	Approved	Marinol increases the expression of Thioredoxin-interacting protein.	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Thioredoxin-interacting protein.	[20]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Thioredoxin-interacting protein.	[21]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Thioredoxin-interacting protein.	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Thioredoxin-interacting protein.	[22]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Thioredoxin-interacting protein.	[23]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Thioredoxin-interacting protein.	[24]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Thioredoxin-interacting protein.	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Thioredoxin-interacting protein.	[26]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Thioredoxin-interacting protein.	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Thioredoxin-interacting protein.	[17]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Thioredoxin-interacting protein.	[28]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Thioredoxin-interacting protein.	[29]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Thioredoxin-interacting protein.	[30]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Thioredoxin-interacting protein.	[17]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Thioredoxin-interacting protein.	[31]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Thioredoxin-interacting protein.	[32]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Thioredoxin-interacting protein.	[33]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Thioredoxin-interacting protein.	[34]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Thioredoxin-interacting protein.	[27]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Thioredoxin-interacting protein.	[35]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Thioredoxin-interacting protein.	[17]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone increases the expression of Thioredoxin-interacting protein.	[17]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Thioredoxin-interacting protein.	[36]
Prasterone	DM67VKL	Approved	Prasterone decreases the expression of Thioredoxin-interacting protein.	[37]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Thioredoxin-interacting protein.	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Thioredoxin-interacting protein.	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Thioredoxin-interacting protein.	[40]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Thioredoxin-interacting protein.	[41]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Thioredoxin-interacting protein.	[42]
Triptolide	DMCMDVR	Phase 3	Triptolide increases the expression of Thioredoxin-interacting protein.	[43]
NVP-LAQ824	DM8JWNA	Phase 3	NVP-LAQ824 increases the expression of Thioredoxin-interacting protein.	[44]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Thioredoxin-interacting protein.	[45]
CERC-801	DM3SZ7P	Phase 2	CERC-801 increases the expression of Thioredoxin-interacting protein.	[46]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Thioredoxin-interacting protein.	[47]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thioredoxin-interacting protein.	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Thioredoxin-interacting protein.	[49]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Thioredoxin-interacting protein.	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Thioredoxin-interacting protein.	[51]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Thioredoxin-interacting protein.	[52]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Thioredoxin-interacting protein.	[53]
PJ34	DMXO6YH	Preclinical	PJ34 increases the expression of Thioredoxin-interacting protein.	[54]
Nobiletin	DM7R3B6	Preclinical	Nobiletin decreases the expression of Thioredoxin-interacting protein.	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Thioredoxin-interacting protein.	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Thioredoxin-interacting protein.	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Thioredoxin-interacting protein.	[25]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Thioredoxin-interacting protein.	[58]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Thioredoxin-interacting protein.	[60]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Thioredoxin-interacting protein.	[61]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Thioredoxin-interacting protein.	[35]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Thioredoxin-interacting protein.	[62]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Thioredoxin-interacting protein.	[63]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Thioredoxin-interacting protein.	[37]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Thioredoxin-interacting protein.	[10]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Thioredoxin-interacting protein.	[64]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Thioredoxin-interacting protein.	[65]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Thioredoxin-interacting protein.	[66]
EPI-001	DMYWV81	Investigative	EPI-001 increases the expression of Thioredoxin-interacting protein.	[67]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Thioredoxin-interacting protein.	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Thioredoxin-interacting protein.	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Thioredoxin-interacting protein.	[59]

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