Details of Drug Off-Target (DOT)

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

• DOT Name: Eukaryotic translation initiation factor 2A (EIF2A)
• Synonyms: eIF-2A; 65 kDa eukaryotic translation initiation factor 2A
• Gene Name: EIF2A
• Related Disease:
  Breast cancer
  Breast carcinoma
  Crohn disease
  Epilepsy
  Inflammatory bowel disease
  Intellectual disability
  Myocardial ischemia
  Plasma cell myeloma
  Hepatitis C virus infection
  Tauopathy
• UniProt ID: EIF2A_HUMAN
• PDB ID: 8DYS
• Pfam ID: PF08662
• Sequence:
  MAPSTPLLTVRGSEGLYMVNGPPHFTESTVFPRESGKNCKVCIFSKDGTLFAWGNGEKVN
  IISVTNKGLLHSFDLLKAVCLEFSPKNTVLATWQPYTTSKDGTAGIPNLQLYDVKTGTCL
  KSFIQKKMQNWCPSWSEDETLCARNVNNEVHFFENNNFNTIANKLHLQKINDFVLSPGPQ
  PYKVAVYVPGSKGAPSFVRLYQYPNFAGPHAALANKSFFKADKVTMLWNKKATAVLVIAS
  TDVDKTGASYYGEQTLHYIATNGESAVVQLPKNGPIYDVVWNSSSTEFCAVYGFMPAKAT
  IFNLKCDPVFDFGTGPRNAAYYSPHGHILVLAGFGNLRGQMEVWDVKNYKLISKPVASDS
  TYFAWCPDGEHILTATCAPRLRVNNGYKIWHYTGSILHKYDVPSNAELWQVSWQPFLDGI
  FPAKTITYQAVPSEVPNEEPKVATAYRPPALRNKPITNSKLHEEEPPQNMKPQSGNDKPL
  SKTALKNQRKHEAKKAAKQEARSDKSPDLAPTPAPQSTPRNTVSQSISGDPEIDKKIKNL
  KKKLKAIEQLKEQAATGKQLEKNQLEKIQKETALLQELEDLELGI
• Function: Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner.
• Tissue Specificity: Widely expressed. Expressed at higher level in pancreas, heart, brain and placenta.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[2]
Epilepsy	DISBB28L	Strong	Biomarker	[3]
Inflammatory bowel disease	DISGN23E	Strong	Posttranslational Modification	[4]
Intellectual disability	DISMBNXP	Strong	Biomarker	[3]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[7]
Tauopathy	DISY2IPA	Limited	Biomarker	[8]

26 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 Eukaryotic translation initiation factor 2A (EIF2A).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[20]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[21]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[23]
Orlistat	DMRJSP8	Approved	Orlistat increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[25]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[26]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[27]
Niflumic acid	DMJ3I1Q	Approved	Niflumic acid increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[28]
Bepridil	DM0RKS4	Approved	Bepridil increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[29]
Nitazoxanide	DMOWLVG	Approved	Nitazoxanide increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[30]
Cerulenin	DM6N4PR	Approved	Cerulenin increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[31]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[26]
Cibenzoline	DMBG0N4	Phase 4	Cibenzoline increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[29]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[32]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[29]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[15]
Ciglitazone	DMAPO0T	Preclinical	Ciglitazone increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[38]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[15]
Paraquat	DMR8O3X	Investigative	Paraquat increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[41]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[5]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[44]
Borrelidin	DMBSQTR	Investigative	Borrelidin increases the phosphorylation of Eukaryotic translation initiation factor 2A (EIF2A).	[46]

20 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 Eukaryotic translation initiation factor 2A (EIF2A).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[18]
Marinol	DM70IK5	Approved	Marinol increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[19]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[18]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[22]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[24]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[11]
Psoralen	DMIZJ8M	Phase 3	Psoralen increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[35]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[37]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[39]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[40]
Manganese	DMKT129	Investigative	Manganese increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[43]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of Eukaryotic translation initiation factor 2A (EIF2A).	[45]

References

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