Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHBQVD5)

• DOT Name: Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)
• Synonyms: 4E-BP1; eIF4E-binding protein 1; Phosphorylated heat- and acid-stable protein regulated by insulin 1; PHAS-I
• Gene Name: EIF4EBP1
• UniProt ID: 4EBP1_HUMAN
• PDB ID: 1EJ4; 1EJH; 1WKW; 2JGB; 2JGC; 2V8W; 2V8X; 2V8Y; 3HXG; 3HXI; 3M93; 3M94; 3U7X; 4UED; 5BXV; 5EKV; 5NVN; 5WBJ; 6BCU; 6BCX
• Pfam ID: PF05456
• Sequence:
  MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLM
  ECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI
• Function: Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  ErbB sig.ling pathway (hsa04012)
  HIF-1 sig.ling pathway (hsa04066)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Cellular senescence (hsa04218)
  Insulin sig.ling pathway (hsa04910)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Herpes simplex virus 1 infection (hsa05168)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Acute myeloid leukemia (hsa05221)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S (R-HSA-72662)
  mTORC1-mediated signalling (R-HSA-166208)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) increases the Blood insulin abnormal ADR of Ethanol.	[66]

25 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 Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[11]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[15]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[26]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[46]
EHT-1864	DMYAMP5	Terminated	EHT-1864 decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[50]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone affects the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[10]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[14]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[16]
Thioridazine	DM35M8J	Approved	Thioridazine decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[18]
Vandetanib	DMRICNP	Approved	Vandetanib decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[19]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[20]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[21]
Epirubicin	DMPDW6T	Approved	Epirubicin increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[22]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[23]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[27]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[28]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[29]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[30]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[31]
BEZ235	DMKBRDL	Phase 2	BEZ235 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[33]
MK-2206	DMT1OZ6	Phase 2	MK-2206 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[34]
GDC-0980/RG7422	DMF3MV1	Phase 2	GDC-0980/RG7422 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[35]
PF-04691502	DMS610L	Phase 2	PF-04691502 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[36]
INK128	DMGO7QT	Phase 2	INK128 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[37]
Antroquinonol	DMRGQVZ	Phase 2	Antroquinonol decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[39]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[40]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[41]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[42]
GSK690693	DMRBVHE	Phase 1	GSK690693 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[35]
GSK2126458	DMM7ZXR	Phase 1	GSK2126458 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[52]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[53]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[55]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[56]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[57]
U0126	DM31OGF	Investigative	U0126 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[58]
USNIC ACID	DMGOURX	Investigative	USNIC ACID decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[59]
BETULIN	DMGQRON	Investigative	BETULIN decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[60]
ABBV-744	DMTEA9C	Investigative	ABBV-744 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[61]
torin 1	DMZD0NA	Investigative	torin 1 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[62]
Thiorphan	DM86LFB	Investigative	Thiorphan decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[63]
KU-55933	DMDT42X	Investigative	KU-55933 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[64]
Torin2	DMC6U93	Investigative	Torin2 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[65]
BAG956	DMWC34B	Investigative	BAG956 decreases the phosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1).	[34]

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