Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIGYVZ)

• DTT Name: HUMAN eukaryotic initiation factor-4A (eIF4A)
• Synonyms: eIF-4A; ATP-dependent RNA helicase Eif4a
• Gene Name: EIF4A1
• BioChemical Class: eIF4A subfamily
• UniProt ID: IF4A1_HUMAN ; IF4A2_HUMAN ; IF4A3_HUMAN
• TTD ID: T86805
• Sequence:
  MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLRGIYAYGFEKPSAIQQ
  RAILPCIKGYDVIAQAQSGTGKTATFAISILQQIELDLKATQALVLAPTRELAQQIQKVV
  MALGDYMGASCHACIGGTNVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFV
  LDEADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFMRDPIRILVKKEE
  LTLEGIRQFYINVEREEWKLDTLCDLYETLTITQAVIFINTRRKVDWLTEKMHARDFTVS
  AMHGDMDQKERDVIMREFRSGSSRVLITTDLLARGIDVQQVSLVINYDLPTNRENYIHRI
  GRGGRFGRKGVAINMVTEEDKRTLRDIETFYNTSIEEMPLNVADLI
• Function: ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon
• Reactome Pathway:
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)
  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)
  ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
eFT226	DMHRCQI	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hippuristanol	DM0PV2Y	T-cell leukaemia	2A90	Investigative	[3]

1 Investigative Agents Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Silvestrol	DM5JKNF	Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[1]

References

• [1] Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Res. 2018 Feb;150:123-129.
• [2] Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase. J Med Chem. 2020 Jun 11;63(11):5879-5955.
• [3] Effects of hippuristanol, an inhibitor of eIF4A, on adult T-cell leukemia. Biochem Pharmacol. 2011 Mar 15;81(6):713-22.