Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8TXA8)

• DOT Name: Eukaryotic translation initiation factor 4B (EIF4B)
• Synonyms: eIF-4B
• Gene Name: EIF4B
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Chronic hepatitis B virus infection
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Estrogen-receptor positive breast cancer
  Hepatocellular carcinoma
  Major depressive disorder
  Renal cell carcinoma
  Skin cancer
  Squamous cell carcinoma
  Triple negative breast cancer
  Neoplasm
• UniProt ID: IF4B_HUMAN
• PDB ID: 1WI8; 2J76; 6FEC
• Pfam ID: PF00076
• Sequence:
  MAASAKKKNKKGKTISLTDFLAEDGGTGGGSTYVSKPVSWADETDDLEGDVSTTWHSNDD
  DVYRAPPIDRSILPTAPRAAREPNIDRSRLPKSPPYTAFLGNLPYDVTEESIKEFFRGLN
  ISAVRLPREPSNPERLKGFGYAEFEDLDSLLSALSLNEESLGNRRIRVDVADQAQDKDRD
  DRSFGRDRNRDSDKTDTDWRARPATDSFDDYPPRRGDDSFGDKYRDRYDSDRYRDGYRDG
  YRDGPRRDMDRYGGRDRYDDRGSRDYDRGYDSRIGSGRRAFGSGYRRDDDYRGGGDRYED
  RYDRRDDRSWSSRDDYSRDDYRRDDRGPPQRPKLNLKPRSTPKEDDSSASTSQSTRAASI
  FGGAKPVDTAAREREVEERLQKEQEKLQRQLDEPKLERRPRERHPSWRSEETQERERSRT
  GSESSQTGTSTTSSRNARRRESEKSLENETLNKEEDCHSPTSKPPKPDQPLKVMPAPPPK
  ENAWVKRSSNPPARSQSSDTEQQSPTSGGGKVAPAQPSEEGPGRKDENKVDGMNAPKGQT
  GNSSRGPGDGGNRDHWKESDRKDGKKDQDSRSAPEPKKPEENPASKFSSASKYAALSVDG
  EDENEGEDYAE
• Function: Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  mTORC1-mediated signalling (R-HSA-166208)
  Deadenylation of mRNA (R-HSA-429947)
  Translation initiation complex formation (R-HSA-72649)
  Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S (R-HSA-72662)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  M-decay (R-HSA-9820841)
  Z-decay (R-HSA-9820865)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Altered Expression	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Skin cancer	DISTM18U	Strong	Altered Expression	[6]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[8]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[9]
Neoplasm	DISZKGEW	Limited	Posttranslational Modification	[10]

16 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 4B (EIF4B).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[18]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[24]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[28]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[29]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[31]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Eukaryotic translation initiation factor 4B (EIF4B).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[20]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Eukaryotic translation initiation factor 4B (EIF4B).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[25]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[30]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[32]
U0126	DM31OGF	Investigative	U0126 decreases the phosphorylation of Eukaryotic translation initiation factor 4B (EIF4B).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Eukaryotic translation initiation factor 4B (EIF4B).	[21]

References

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